MXPA01006896A - Cyclic compound. - Google Patents

Abstract

A compound of formula (I) in which R1 is lower alkyl, halogen, optionally substituted heterocyclic group or optionally substituted aryl, R2 is carboxy, protected carboxy or amidated carboxy, Ar is optionally substituted aryl or optionally substituted heterocyclic group, A is lower alkylene, X is oxa or a single bond, Y is thia, sulfinyl or sulfonyl, Z is methylene, thia, sulfinyl or sulfonyl, m and n are each an integer of 0 to 6, and 1<=m+n<=6, or its salt, which is useful as an inhibitor of matrix metalloproteinases (MMP) or tumor necrosis factor alpha (TNF alpha).

Description

TIOPIRAM COMPOUNDS AS MATRIX METALOPROTEINASE INHIBITORS (MMP) Field of the Invention The present invention relates to novel compounds and their pharmaceutically acceptable salts thereof. More particularly, it relates to novel compounds and pharmaceutically acceptable salts thereof, which are useful as inhibitors of matrix metalloproteinases (hereinafter referred to as MMPs) or the production of tumor necrosis factor factor a ( hereinafter referred to as TNF a), to pharmaceutical compositions comprising the same, to the use of the same medicaments, and to methods for using the same in a therapeutically manner in the treatment and / or prevention of diseases mediated by MMP or TNF a. BACKGROUND OF THE ART Some compounds that are useful as inhibitors of metalloproteinase, or the like, are known (WO 97/20824, etc.). Disclosure of the Invention An object of the present invention is to provide novel and useful cyclic compounds and pharmaceutically acceptable salts thereof, and to provide a process for preparing the novel cyclic compound and salts thereof, which have pharmacological activities such as inhibitory activity of MMP or TNF a, and the like. Another object of the present invention is to provide a pharmaceutical composition comprising, as an active ingredient, the cyclic compound or a pharmaceutically acceptable salt. Another object of the present invention is to provide the use of the cyclic compounds and pharmaceutically acceptable salts thereof as medicaments for the therapeutic prophylactic treatment of diseases mediated by MMP or TNF.Also another object of the present invention is 15 to provide a method for using the same treatment and / or preventing diseases mediated by MMP or TNFα in mammals, especially humans. The compounds of the present invention have inhibitory activity in MMP or the production of TNFα, and are useful in the treatment and / or prevention of diseases such as cerebrovascular disorder, arthritis, cancer, tissue ulceration, decubitus ulcer , restenosis, periodontal disease, bullous epidermolysis, scleritis, psoriasis and other diseases that are characterized by matrix metalloproteinase activity, as well as AIDS, sepsis, septic shock and other diseases caused by the production of TNF a. There are a number of structurally related metalloproteases which effect the decomposition of structural proteins. Metalloproteases that degrade the matrix, such as gelatinase (MMP-2, MMP-9), stromelysin (MMP-3) and collagenase (MMP-1, MMP-8, MMP-13), are involved in matrix degradation of tissues and are implicated in many pathological conditions involving abnormal connective tissue and metabolism of basement membrane matrix, such as arthritis (e.g., osteoarthritis and rheumatic arthritis, etc.), brain disease (e.g., cerebrovascular disorder) , etc.), tissue ulceration (eg corneal, epidermal and gastric ulceration, etc.), healing of abnormal wounds, periodontal disease, bone diseases (eg Paget's disease and osteoporosis, etc.), tumor metastasis or invasion and HIV infection. A tumor necrosis factor is recognized that is involved in many infections and autoimmune diseases. It is also shown that TNF is the most important mediator of the inflammatory response seen in sepsis and septic shock. The compounds of the objective of the present invention are novel and can be represented by the following formula (I): Rl-X-Ar- (CH2) m (CH2) n-R2 i) wherein R1 is lower alkyl, halogen, optionally substituted heterocyclic group or optionally substituted aryl, R2 is carboxy, protected carboxy or amidated carboxy, Ar is optionally substituted aryl or optionally substituted heterocyclic group, A is lower alkylene, X is oxa or a single bond, Y is thio, sulfinyl or sulfonyl, Z is methylene, thio, sulfinyl or sulfonyl, myn are each a number whole of between 0 and 6, and 1 < m + n < 6, and its salt. The compounds of the object of the present invention can be prepared by the following processes: Process 1 Removal of the group r? R? »Vi -protected Rl-X-Ar- (CH2) CCHH2) n-R (I-a) (I-b) Or a salt thereof Process 2 (ID OR a salt of it -? - Ay-, c "2) (C - COOH (I-b) OR a salt of the same Process 3 (I-c) Or a salt thereof (I-) 0 a salt thereof Process 4 ina, or its derivative reactive or a salt thereof of the carboxy-group, or a salt thereof (I-e) Or a salt 1 daoe7 mmi, -smo Process 5 Rl (III) Or a salt of the mispo (I-f) 0 a salt thereof Process 6 and z amine optically Ri-X-Ar- (CH2) mXX. (CH2) n-COOH active (I-b) or its reagent derivative to the carboxy group, or a salt thereof R1-X-Ar- (CH2) m .X ", (CH2) n-R2 d-g) Or a salt of mmiism (I-) 0 a salt thereof (I-í) Or a salt of it Process 8 (I-j) Or a salt thereof (I-) Or a salt thereof (I-c) Or a salt thereof Rl-X-Ar- (CH2) rrXXCH2) n- 2 (I-) OR a salt thereof Proce (VI) Or a salt thereof íl-m) 0 a salt thereof Or a salt of it -X-Ar- (CH), m (CH2) n-R2 I-n! Or a salt of the same Process 12 (IX) 0 or "salt thereof (I-o) Or a salt of the same Process 13 Amide., I? N (I-P) or its reagent derived from the carboxy group, or a salt thereof (i - -g) 0 an i salt of the same Process 14 z Rl-X-Ar- (CH 2) m- > (CH2) n-R2 il-r) or its reactive derivative to the amine group, or a salt thereof (I-s) Or a salt thereof (I-t) Or a salt thereof R1-X-Ar- (CH2) m. ^ iCH 2) n-R2 (I-r 0 A salt of it Process 16 (I-u) Or a salt of it (I-v) Or a salt thereof Y z Ri-X-Ar- (CH2) m CH?) "- R: oxidation, k (I-w) or a salt thereof Y z Rl-X-Ar- (CH2) mX. (CH2) n-R2 (I-x) Or a salt thereof Process 18 Reduction d-y) Or a salt thereof Y Z Rl-X-Ar- (CH2) mX? CH2) n. R2 (I-z) Or a salt of the same Process 19 (I-aa) 0 a salt thereof (I-ab) O A salt of it Process 20 (I-v) Or a salt thereof ; 1-X-Ar- (CH2) rtXXcH2) n-R2 (I-ac) OR a salt thereof (XI) or a salt thereof (I-ad) O A salt of it Process 22 (I-ae) Or a salt thereof R1-X-Ar- (CH2) CH2) n-R2 (I-P) OR a salt thereof (I-af) OR a salt thereof (I-ag) Or a salt thereof wherein R1, R2, Ar, A, X, Y, Z, and n are, each as defined above, R a is haloaryl or halo, R x b aryl, R x c is aryl at least substituted by optionally substituted aryl Rld is aryl having at least one carboxy portion, R1e is aryl having at least one amido moiety, R1f is aryl having at least one amino moiety, R1g is aryl having at least one acylamino moiety, is aryl which is has at least one protected amino moiety, RiL is aryl having at least one protected hydroxy moiety, R1 is aryl having at least one hydroxy moiety, Rlk is aryl having at least one thio moiety, R1! is aryl having at least one sulfinyl or sulfonyl moiety, R 1, is aryl having at least one formyl moiety, R 1r? is aryl having at least one hydroxymethyl portion, Rx0 is aryl having at least one vinyl moiety, Rxp is aryl having at least one 1,2-dihydroxyethyl moiety, R1q is aryl having at least one acyloxy moiety , R1 ,. is aryl having at least one protected carboxy moiety, R xs is aryl having at least one halo (lower) alkanoyl portion, R x is aryl having at least one substituted lower alkanoyl ring moiety, R 20 is protected carboxy, R2b is optically active amide, R2C is protected carboxy, R3 is hydrogen or hydroxy protecting group, R3a is hydroxy protecting group, R4 is optionally substituted aryl R5 and R6 are each hydrogen or combine together to form lower alkylene, Yd is uncle , sulfinyl or sulfonyl, Za is methylene, uncle, sulfinyl or sulfonyl which provide at least one Yd and Za is uncle or sulfinyl, Yb is thio, sulfinyl or sulfonyl, Zb is methylene, uncle, sulfyl or sulfonyl which provide at least one Yb and Zb which is sulfinyl or sulfonyl, L is a leaving group, and m1 is an integer of 1 and 6. The starting compounds that are used in the above processes can be prepared according to the following preparations or by a conventional method. Suitable salts of the subject compounds (I) to (I-ae) may be conventional non-toxic pharmaceutically acceptable salts and include an acid addition salt, such as an organic acid salt (e.g., acetate, tpfluoacetate, maleate, tartrate , fumarate, methanesulfonate, benzenesulfonate, formate, toluenesulfonate, etc.), an inorganic acid salt (for example, hydrochloride, bromihydrate, iodide, sulfate, nitrate, phosphate, etc.), or a salt with a base such as an amino acid ( for example, argimna, aspartic acid, glutamic acid, etc.), an alkali metal salt (eg, sodium salt, potassium salt, etc.), an alkaline earth metal salt (eg, calcium salt, magnesium salt, etc.), an ammonium salt, an organic base salt (eg, trimethylamine salt, triethylamine salt, pyridine salt, picolma salt, dicyclohexylamine salt, N, N'-dibenzylethylenediamine salt , etc.), or similar ones. The objective compounds and pharmaceutically acceptable salts thereof may include solvates, such as the inclusion compounds (eg, hydrate, etc.). Suitable examples and illustrations of the definitions, which the present invention includes within its scope and which are shown above and in the subsequent descriptions of the present specification, are as follows. By the term "lower" is used to indicate 6 carbon atoms, preferably above 4 carbon atoms, unless otherwise indicated. Suitable "aryl" and aplo portion in the term "optionally substituted aryl" may include an aryl having 6 to 10 carbon atoms, such as phenyl, tolyl, xylyl, cumenyl, mesityl, naphthyl and the like, preferably phenyl and naphthyl . The convenient "optionally substituted aplo" may include the aryl mentioned above which is substituted by the group consisting of the following (Al) to (A35); (Al) halogen, (A2) lower alkyl, (A3) lower alkoxy, (A4) halo (lower) alkyl, (A5) halo lower alkoxy, (A6) lower alkenyl, (A7) acyl, (A8) alkylthio lower, lower alkylsulfinyl, lower alkylsulphonyl, (A9) C6-C10 aryl (AlO) C6-C10 aryl halo, (All) hydroxy, (A12) hydroxyalkyl (lower), protected lower hydroxyalkyl, (A13) a ino, ( A14) carboxy, (A15) carboxy protected, (A16) nitro alkenyl (lower), (A17) lower alkylenedioxy, (Al8) acylamino, (Al9) nitro, (A20) aryl (C6-C1C) alkoxy (lower) , (A21) carbamoylalkenyl (lower) optionally N- substituted by the group consisting of lower alkyl, C6-C10 aryl lower alkoxy-C6-C10 aryl and halo aplo C6-C10), (A22) lower alkylaminocarbonyloxy, (A23) ) lower alkanoyloxy, (A24) lower alkoxy alkanoyloxy (lower), (A25) lower alkoxycarbonyloxy, (A26) lower alkenyloxy optionally substituted by heterocyclic group of (1) to (14) precedents, (A27) lower cycloalkanecarbonyloxy, (A28) lower alkoxy substituted by the group consisting of carboxy, protected carboxy, lower alkanoyl, lower cycloalkanecarbamoyl, and lower alkylcarbamoyl, (A29) lower alkylcarbamoyloxy lower alkyl, (A30) lower alkoxycarbonylamino alkyl (lower), (A31) ammoalkyl (lower), (A32) lower alkylcarbamoyl lower alkyl, (A33) heterocyclic carbonylamino, the heterocyclic group is selected from the above (1) to (14) which are optionally substituted by the N-protecting group, (A34) the heterocyclic groups mentioned previously (1) to (14) are optionally substituted by lower alkyl and (A35) oxo. The "heterocyclic group" desirable in the term "optionally substituted heterocyclic group" means saturated or saturated monocyclic or polycyclic heterocyclic group., which contains at least one heteroatom such as an oxygen atom, a sulfur atom, a nitrogen atom or the like. Preferred heterocyclic groups are the following (1) to (14): (1) 3 to 8 membered, preferably 5 or 6 membered, heteromonocyclic group containing from 1 to 4 nitrogen atoms (pyrrolyl, pyrrolmyl, ylidazolyl, pyrazolyl, pyridyl and its N-oxide, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl (for example, 4H-1,2,4-triazolyl, lH-2,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.), tetrazolyl (e.g., lH-tetrazolyl, 2H-tetrazole, etc.), dihydrotriazinyl (e.g., 4,5-dihydro-l, 2,4-triazinyl, 2,5-dihydro-l, 2,4-triazinyl, etc.), and the like; (2) 3 to 8 membered saturated, preferably 5 or 6 membered, heteromonocyclic group containing from 1 to 4 nitrogen atoms, (azetidinyl, pyrrolidinyl, imidazolidinyl, piperidinyl, piperidino, pyrazolidinyl, piperazinyl, and the like); (3) 3 to 8 membered unsaturated heteromonocyclic group, preferably 5 or 6 membered, containing 1 to 2 sulfur atoms (thienyl, and the like); (4) condensed unsaturated heterocyclic group (preferably bicyclic) of 7 to 13 members, preferably 9 to 10 members, containing from 1 to 5 nitrogen atoms (indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl, tetrazolopyridyl, tetrazolopyridazinyl (for example, tetrazolo [1, 5-b] pyridazinyl, etc.), dihydrotriazolopyridazinyl, and the like); (5) 3 to 8 membered unsaturated heteromonocyclic group, preferably 5 to 6 membered, containing 1 or 2 oxygen atoms (furyl, and the like); (6) saturated heteromonocyclic group of 3 to 8 members, preferably 5 to 6 members, containing 1 or 2 oxygen atoms (oxolanyl, and the like); (7) 3 to 8 membered unsaturated heteromonocyclic group, preferably 5 to 6 membered, containing 1 or 2 oxygen atoms and 1 or 3 nitrogen atoms (oxazolyl, isoxazolyl, oxadiazolyl (e.g., 1,2, 4- oxadiazolyl, 1,3,4-oxadiazolyl, 1, 2, 5-oxadiazolyl, etc.), and the like); (8) fused unsaturated (preferably bicyclic) heterocyclic group, of 7 to 13 members, preferably 9 to 10 members, containing 1 or 2 oxygen atoms (benzofuranyl, benzodihydrofuranyl, benzodioxolemyl, and the like); (9) condensed (preferably bicyclic) condensed heterocyclic group, from 7 to 13 members, preferably from 9 to 10 members, containing 1 or 2 sulfur atoms (benzothienyl, dihydrobenzothienyl, and the like); (10) saturated 3 to 8 membered heteromonocyclic group, preferably 5 to 6 membered, containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms (morpholyl, morphol, and the like); (11) condensed (preferably bicyclic) condensed heterocyclic group of 7 to 13 members, preferably 9 to 10 members, containing 1 or 2 oxygen atoms and 1 or 3 nitrogen atoms (benzoxazolyl, benzoxadiazolyl, and the like); (12) 3 to 8 membered saturated heteromonocyclic group, preferably 5 to 6 members, containing 1 or 2 sulfur atoms and 1 or 3 nitrogen atoms (thiazolyl, 1,2-thiazolyl, thiazolyl, thiadiazolyl (for example, 1, 2, 4-toluene, 1,3,4-thiadiazolyl, 1, 2, 5-t-ad? Aolol, 1,2,3-thiadiazolyl, etc.), and the like ); (13) saturated 3 to 8 membered heteromonocyclic group, preferably 5 to 6 membered, containing 1 or 2 sulfur atoms and 1 or 3 nitrogen atoms (thiazolidinyl, and the like); (14) fused unsaturated (preferably bicyclic) heterocyclic group, of 7 to 13 members, preferably 9 to 10 members, containing 1 or 2 sulfur atoms and 1 or 3 nitrogen atoms (benzothiazolyl, benzothiadiazolyl, and the like); etc. These heterocyclic groups may have one or more substituents. Examples of substituents for substituted heterocyclic groups may be the same as "optionally substituted aryl" (previously mentioned in (Al) to (A35)). Convenient "lower alkyl" may include a straight or branched alkyl having 1 to 6 carbon atoms, and exemplified by methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertbutyl, pentyl, hexyl and the like, and most preferred is methyl for R1. Convenient "lower alkenyl" may include straight or branched alkenyl having 2 to 6 carbon atoms, and exemplified by ethenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 1-pentenyl, 2-pentenyl and Similar. Convenient "lower alkoxy" may include a straight or branched alkenyl having 1 to 6 carbon atoms, and exemplified by methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, terbutoxy, pentyloxy, terpentyloxy, hexyloxy and the like. The convenient "hydroxy protecting group" can include a conventional protecting group, for example, substituted lower alkyl, such as lower alkoxy lower alkyl, (e.g., methoxymethyl), lower alkoxy lower alkoxy, lower alkyl (e.g. methoxyethoxymethyl) and unsubstituted or substituted (lower) arylalkyl (for example, benzylnitrobenzyl); acyl such as lower alkanoyl (eg, acetyl, propionyl, pivaloyl), aroyl (eg benzoyl, fluorencarbonilo), lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl) , arylalkoxycarbonyl (lower) alkyl substituted or unsubstituted (e.g. benzyloxycarbonyl, bromobenzyloxycarbonyl), arensulfonilo (eg benzenesulfonyl, tosyl) and alkanesulfonyl (eg methanesulfonyl, ethanesulfonyl), trialkylsilyl (lower) alkyl (eg tnmetilsililo); tetrahydropyranyl; and the like, preferably tetrahydropyranyl. Convenient "halogen" includes fluorine, bromine, chlorine and iodine. The appropriate acyl and acyl moiety of "acilammo" include acyl such as aliphatic acyl, aromatic acyl, heterocyclic acyl and aliphatic acyl substituted by group (s) aromatic (s) or heterocyclic (s) derived (n) of carboxylic acids, carbonic, sulphonic and carbamic. Alif acyl attic includes acícliclos or cyclic, saturated or msaturados, for example, alkanoyl such as lower alkanoyl (e.g., formulate, acetyl, propionyl, butylyl, isobutylyl, valeryl, isovaleryl, pivaloyl, hexanoyl, etc.); alkylsulfonyl such as lower alkyl fonyl (for example, mesyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, pentylsulfonyl, hexylsulfonyl, etc.); carbamoyl, N-alkylcarbamoyl (for example, methylcarbamoyl, ethylcarbamoyl, etc.); alcoxicarbomlo as lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, etc.), alkenyloxycarbonyl such as lower alkenyloxycarbonyl (eg viniloxicarbomlo, allyloxycarbonyl, etc.), alkenoyl such as lower alkenoyl (eg acploilo , methacryloyl, crotonoyl, etc.), cycloalkanecarbonyl such as cycloalkanecarbonyl (lower) (eg, cyclopropanecarbonyl, cyclopentanecarbonyl, cyclohexanecarbonyl, etc.), and the like. The aromatic acyl may include aroyl C6-C10 (eg benzoyl, toluoyl, xyloyl, etc.), N-arylcarbamoyl of (C6-C10) (for example, Nf enilcarbamoilo, N- tol i lcarbamoi what, N-naf ti lcarbamoi lo, etc.), C6-C10 arenesulfonyl (for example, benzenesulf onyl, tosyl, etc.), and the like. The heterocyclic acyl may include heterocyclic carbonyl (e.g., furoyl, tenoyl, nicotinoyl, isonicotinoyl, thiazolylcarbonyl, thiadiazolylcarbonyl, tetrazolylcarbonyl, etc.), and the like. The aliphatic acyl substituted by aromatic group (s) can (a) include aralkanoyl such as phenylalkanoyl (lower) (for example phenylacetyl, phenylpropionyl, phenylhexanoyl, etc.), aralkoxycarbonyl such as phenylalkoxycarbonyl (lower) (for example, benzyloxycarbonyl, phenethyloxycarbonyl, etc.), aryloxyalkanoyl such as phenoxyalkanoyl (lower) (for example, f-enoxyacetyl, phenoxypropionyl, etc.), and the like. The aliphatic acyl substituted by heterocyclic group (s) may (n) include heterocyclic alkanoyl such as heterocyclic (lower) alkanoyl (eg, thienylacetyl, imidazole lacetyl, f uri lacetyl, tetrazolylacetyl, thiazolylacetyl, thiadiazolylacetyl, thienylpropionyl , thiadiazolylpropionyl, etc.), and the like. These acyl groups can also be substituted by one or more convenient substituents, such as for the "optionally substituted aplo" (mentioned above (Al) or (A35)). Suitable "protected carboxy" includes carboxy-labeled carboxy where "esterified carboxy" is defined below. Suitable examples of the ester moiety of the esterified carboxy are lower alkylester (for example, methyl ester, ethyl ester, propyl ester, isopropyl ether, butyl ester, isobutyl ester, terbutyl ester, pentyl ester, hexyl ester, etc.) and the like, which may have, at least a convenient substituent. Examples of the substituted lower alkyl ester are lower alkanoyloxy lower alkyl ester [eg, acetoxymethylester, propionyloxymethyl ester, butycloxymethyl ester, valeryloxymethyl ester, pivaloyloxymethyl ester, hexanoyloxymethyl ester, 1- (or 2-) acetoxyethyl ester, 1- (or 2- or 3-acetoxypropyl ester, 1- (or 2- or 3- or 4-) acetoxybutylester, 1- (or 2) prop? On? Lox? Et? Lester, l- (or 2- or 3-) prop? On? Lox? Prop? Ester, 1- (or 2-) but? R? Lox? Et? Lester, 1 - (or 2-) isobutyryloxyethyl ester, 1- (or 2-) p? valo? lox? et? lester, 1- (or 2-) hexanoyloxyethyl ester, isobutyryloxymethyl ester, 2-et? lbut? plox? met? lester, 3, 3-dimethylbutyloxymethylester, 1- (or 2-) pentane? Lox? Ethersethers, etc.,], lower alkanesulfonyl lower alkyl ester (eg, 2-mesylethylester, etc.), mono (or di or tri) haloalkylester (lower) (for example, 2-iodoethyl ester, 2,2,2-trichloroethyl ester, etc.); alkoxycarbonyloxy lower alkyl ester (lower) [e.g., methoxycarbonyloxymethyl ester, ethoxycarbonyloxymethyl ester, propoxycarbonyloxymethyl ester, tert-butoxycarbonyloxymethyl ester, 1- (or 2-) methoxycarbonyloxyethyl ester, 1- (or 2-) ethoxycarbonyloxyethyl ester, l- (or 2-) isopropoxycarbonyloxyethyl tert, etc.], phthalidylidene alkyl ester (lower), lower (5-lower alkyl-2-oxo-l, 3-dioxol-4-yl) lower alkyl ester [e.g., (5-methyl-2-oxo-l, 3-dioxol-4-yl) methyl ester, (5-ethyl-2-oxo-l, 3-dioxol-4-yl) methyl ester, (5-propyl-2-oxo-l, 3-dioxol-4-yl) ethyl ester, etc.]; lower alkenylester (for example, vinylester, allylester, etc.); lower alkynylester (for example, ethynylester, propynylester, etc.); lower aralkyester which may have at least one convenient substituent (eg, benzyl ester, 4-methoxybenzyl ester, 4-nitrobenzyl ester, phenethyl ester, tritylester, benzydryester, bis (methoxyphenyl) methyl ester, 3,4-dimethoxybenzyl ester, 4-hydroxy-3) , 5-diterbutylbenzyl ester, etc.); arylester which may have at least one convenient substituent (eg, phenylester, 4-chlorophenylester, tolylester, tertiary butyl phenyl ester, xylylester, mesitylester, cumenylester, etc.); phthalidyl ester; and similar. More preferred example of the protected carboxy which is defined may be C1-C4 alkoxycarbonyl, and the most preferred may be methoxycarbonyl, ethoxycarbonyl, and t-butoxycarbonyl for R2. The "amidated carboxy" can be referred to one of those mentioned below. Suitable examples of the amidated carboxy may include optionally substituted carbamoyl, such as: -carbamoyl, -N-hydroxycarbamoyl, -N- (protected hydroxy) carbamoyl, wherein the hydroxy protecting group may be the same as mentioned above (e.g., tetrahydropyranyl) , etc.), - mono (or di) alkylcarbamoyl (lower) wherein the lower alkyl group may be the same as mentioned above (eg methylcarbamoyl), ethylcarbamoyl, isopropylcarbamoyl, butylcarbamoyl, 3-methylbutylcarbamoyl, isobutylcarbamoyl, pentylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl, etc.), -N- (arylalkyl (lower)) carbamoyl, such as phenylalkyl carbamoyl (lower) (for example 1-phenylethylcarbamoyl, (R ) - (+) -1-phenylethyl, etc.), - (C3-C7) alkylcarbamoyl cycle (for example cyclohexylcarbamoyl, etc.), carbamoyl substituted by amino or dialkyl amino (lower) [for example N-aminocarbamoyl, N - (dimethylamino) carbamoyl, etc.], - lower alkylene-aminocarbonyl (for example pyrrolidomethyl-1-carbonyl, hexahydro-lH-azepm-1-licarbonyl, etc.), the alkylene which is optionally substituted by carboxy or protected carboxy, as mentioned above, such as lower alkoxycarbonyl [e.g. carboxy pyrrolidomethylcarbonyl], (ethoxycarbonyl) pyrrolidomethylcarbonyl; , (ethoxycarbonyl) pyrrolidm-1-carbonyl, etc.], or the lower alkylene is optionally interrupted by other (s) hete atom (s) such as nitrogen, oxygen or sulfur (for example morpholinecarbonyl, etc.). ) - lower alkylsulfonylcarbamoyl (for example methylsulfonylcarbamoyl, etc.), -arensul fonylcarbamoyl (for example benzenesulfonylcarbamoyl, etc.), and the like. Preferred example of amidated carboxy thus defined may be: N-hydroxycarbamoyl, N-tetrahydropyranyloxycarbamoyl, and N- (phenylethyl) carbamoyl for R2. Suitable "leaving group" may include halogen as mentioned above, acyloxy, such as sulfonyloxy (eg, mesyloxy, tosyloxy, etc.), alkoxy (for example, terbutoxy, etc.), aralkoxy (for example, benzyloxy, etc.), and the like, preferably halogen and the most preferred is bromine. Suitable "lower alkylene" may include linear or branched, such as methylene, ethylene, trimethylene, propylene, tetramethylene, ethylethylene, pentamethylene, hexamethylene, and the like, in which the most preferred may be C 1 -C 4 alkylene, and preferred may be ethylene, 1-methyltrimethylene, and trimethylene. The "halo (lower alkyl)" suitable as mentioned above for the lower alkyl may be substituted by halogen as mentioned above, wherein the most preferred one may be haloalkyl (Cx-C ,,). The "halo (lower alkoxy)" convenient as envisioned above the lower alkoxy can be substituted by halogen, as mentioned above, in which the most preferred one can be halo (C 2 -C) alkoxy. Suitable "lower alkylthio" can be thio group substituted by lower alkyl as mentioned above, in which the most preferred one can be C 1 -C alkylthio (for example methylthio, ethylthio, etc.). Suitable "lower alkylsulfinyl" may include methylsulfinyl, ethylsulfinyl, and the like, wherein the most preferred may be Cx-C alkylsulfinyl (for example methylsulfinyl, etc.). Suitable "lower alkylsulfonyl" may include methylsulfonyl, ethylsulfonyl, and the like, in which the most preferred is alkylsulfonyl of Cj.-C (for example methylsulfonyl, etc.). The convenient "haloaryl" as mentioned above can be replaced by halogen, the most preferred one being halo (C6-C10), and the most referred is 4-fluophenyl. The "hydroxy (lower) alkyl" convenient as mentioned above, the lower alkyl may be substituted by hydroxy as mentioned above, wherein the most preferred one may be hydroxy (C 4) alkyl. The "hydroxy (lower) alkyl protected" convenient as mentioned above hydroxyalkyl group (lower) protected by a conventional hydroxy protecting group such as acyl, (lower alkyl) (diaryl) silyl group (for example (t-butyl) (diphenyl) silyl, etc.), and the like. Suitable "aryl-lower alkoxy" may include benzyloxy, phenylethoxy, and the like, in which the most preferred one may be phenyl-lower alkoxy (02-04) (for example benzyloxy, etc.). Suitable "carbamoylalkenyl (lower)" may include carbamoylethenyl, carbamoylallyl, and the like, in which the most preferred may be carbamoylalkenyl of (C ^ -C) for example carbamoylethenyl, etc. ).

The term "convenient lower alkoxyaryl" may include methoxyphenyl, ethoxyphenyl, and the like, in which the most preferred may be Cx-C4 alkoxyphenyl (for example methoxyphenyl, etc.). More preferred examples of "lower carbamoylalkenyl" optionally N-substituted by the group consisting of lower alkyl, aryl, lower alkoxyaryl and haloaryl "which may include lower alkylcarbamoyl (lower) alkenyl (e.g. carbamoylethenyl, me ti 1 carb amo i 1 et al 1 i, eti 1 ca rb amo i 1 eteni 1 o, propyl carbamoi letenilo, isopropicarbamoiletenilo, dimetilcarbamoiletenilo, etc.), arilcarbamoilalquenilo of C6-C10 (inferior) (for example f enilcarbamoiletenilo, etc.), alkoxi inferior of (C6-C10) arylcarbamoylalkenyl (lower) (for example methoxyprylocarbamoylethenyl, etc.), haloarylcarbamoylalkenyl (lower) (for example p-halophenylcarbamoylethenyl, etc.), and the like. Suitable "lower alkylaminocarbonyloxy" may include methylaminocarbonyloxy, ethylaminocarbonyloxy, and the like, in which the most preferred one may be alkylaminocarbonyloxy of C? -C4 (for example methylaminocarbonyloxy, ethylaminocarbonyloxy, etc.). Convenient "lower alkanoyloxy" may include acetoxy, propanoyloxy, and the like, in which the most preferred may be C: -C4 alkanoyloxy (for example propanoyloxy, etc.). The "lower alkanoyloxy (lower) alkoxy" may conveniently include methoxyacetyloxy, ethoxyacetyloxy, and the like, in which the most preferred may be C1-C4 alkoxy alkanoyloxy of (Ci-C (for example methoxyacetyloxy, etc.) Convenient "lower alkoxycarbonyloxy" may include methoxycarbonyloxy, ethoxycarbonyloxy, and the like, which C4-C4-alkoxycarbonyloxy (eg, ethoxycarbonyloxy, etc.) may be most preferred. "Convenient" lower alkenyloxy "may include acryloyloxy, and the like, in which the most preferred may be C2-C4 alkenoyloxy (eg. example, acryloyloxy, etc.) Preferred examples of "lower alkenoyloxy optionally substituted by heterocyclic group may include lower alkenoyloxy optionally substituted by the above-mentioned heterocyclic group (1) (e.g. pyridyl, etc.), such as pyridylacryloyloxy, and the like. Suitable "lower cycloalkanecarbonyloxy" may include C3-C7 cycloalkanecarbonyloxy such as cyclopropanecarbonyloxy, cyclobutanecarbonyloxy, and the like, in which the Preferred may be C4-C6-alkanedcarbonyloxy (eg, cyclopropanecarbonyloxy, etc.). Suitable "lower cycloalkanecarbamoyl" may include C-C7 cycloalkanecarbamoyl such as cyclopropanecarbamoyl, cyclobutanecarbamoyl, and the like, wherein the most preferred may be C4-C6 cycloalkanecarbamoyl (e.g. cyclopropanecarbamoyl, etc.). Suitable "lower alkylcarbamoyl" may include methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, and the like, in which the most preferred may be C 1 -C 4 alkylcarbamoyl (eg, methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, etc.). Preferred examples of "lower alkoxy substituted by the group consisting of carboxy, protected carboxy, lower alkanoyl, lower cycloalkanecarbamoyl, lower alkylcarbamoyl may include arboxialkoxy (lower) (eg carboxymethoxy, etc.) lower alkoxycarbonyl lower alkoxy (eg, ethoxycarbonylmethoxy) , butoxycarbonylmethoxy, etc.), lower alkoxy lower alkoxy (for example propanoyl ratoxy, etc.), lower cycloalkanecarbamoyl lower alkoxy (for example cyclopropylcarbamoylmethoxy, etc.), lower alkoxycarbamoyl lower alkoxy (for example methylcarbamoylmethoxy, ethylcarbamoylmethoxy, propylcarbamoylmethoxy, etc.), and the like The expression "alkylcarbamoyloxy lower alkyl (lower) "convenient may include methylcarbamoyloxymethyl, ethylcarbamoyloxymethyl, and the like, in which the most preferred may be C 1 -C 4 alkylcarbamoyloxy (C 1 -C 4) alkyl (eg methylcarbamoyloxymethyl, t-butoxycarbonylaminomethyl, etc.). lower) "may include aminomethyl, aminoethyl, and the like, in which the most preferred one may be (Cx-C4) aminoalkyl (for example aminomethyl, etc.)." Suitable "lower alkyl (lower) alkylcarbamoyl" may include methylcarbamoylmethyl , methylcarbamoylethyl, ethylcarbamoylmethyl, ethylcarbamoylethyl, and the like, in which the most preferred one can be C 1 -C 4 alkylcarbamoyl (Cx-C4) (for example methylcarbamoylmethyl, etc.). Suitable "heterocyclic carbonylamino" may include carbonylamino group substituted by the above-mentioned heterocyclic group (2), (4) and (5) (for example pyrrolidinyl, teretahydroisoquinolyl, fuplo, etc.) such as pyrrolidinium-locarbonylamino, 1,2, 3, -teretahydroisoquinolylcarbonylamino, furylcarbonylamino, and the like. Preferred examples of "optionally substituted heterocyclic carbonylamino" may include the above-mentioned heterocyclic carbonylamino, optionally the heterocyclic group is replaced by an N-protecting group (for example acyl such as alkoxycarbonyl, etc.), such as pyrrolidinylcarbonylamino, 1,2,3 , 4- teretahydroisoquinolyl carbo or lamino, (N- (t-butoxycarbonyl) -1, 2, 3, 4-teretahydroisoquinolyl) -carbonylamino, furylcarbonylamino, and the like.

The "convenient (lower) nitroalkenyl" can include the above-mentioned lower alkenyl substituted by nitro, in which the most preferred one can be nitro-alkenyl of (C2-C4). Convenient "lower alkylenedioxy" may include a linear or branched, such as methylenedioxy, ethylenedioxy, trimetyl 1-endy oxy, propy1-endyloxy, tetramethylenedioxy, ethyleylenedioxy, pentamethylenedioxy, hexamethylenedioxy, and the like, in which the most preferred one may to be alkylene dioxy of Cx-C4. The convenient "amido" may include the same as for the "carboxy amidated" group, and preferably lower alkylcarbamoyl, and the most preferred is ethylcarbamoyl. Suitable "acylamm" may include the amino group substituted by acyl, as mentioned above. The convenient "substituted amine" may include the ammo group substituted by the above-mentioned substituents (A2) to (A12), (A14) to (A17), (A20) to (A32) and (A34). Preferred examples may be hydroxy alkylamine (lower) (for example hydroxyethylamine, etc.), the above-mentioned heterocyclic group containing N (for example morpholmo, etc.), lower alkenylamma (for example alilamma, etc.), arylalkylamine of C6-C10 (lower), example benzylamine, etc.), lower alkylamine (for example t-butylamine, pentylamine, etc.), heterocyclic (lower) alkylamine, such as pyridylalkylamine (lower) (for example pyridylomethylamine, etc.), lower alkoxy lower alkylamine ( for example ethoxyethylamine, etc.), and the like. Preferred examples of the formula: and similar (i) one of the preferred ones may be the compounds (I), wherein yn are each 0 or 1, and (ii) the most preferred compounds may be those indicated in subparagraph (i) above, where A is ethylene, 1-methyltrimethylene, or trimethylene. The most preferred subject compounds (I) are: [iii) compounds (I), which have the following formula wherein a group of the formula is one of the following formulas R1 is an alkyl, phenyl, halophenyl, or phenyl (phenyl) (halo) lower, R2 is a carboxyl or hydroxyaminocarbonyl, and m and n are each an integer of 0 or 1, and m + n = l. (iv) the compounds (I) having the following formula: where a group of the formula: is R 2 is a carboxyl or hydroxyaminocarbonyl, m and n are each an integer of 0 or 1, and m + n = 1, R 1 is halogen; heterocyclic group consisting of pyridyl, thienyl, furyl, benzofuranyl or benzothienyl, wherein the heterocyclic group is optionally substituted by the group consisting of lower alkanoyl, lower alkyl, lower alkoxy, lower alkoxycarbonylamino and lower alkylcarbamoyl; naphthyl or phenyl optionally substituted by the group consisting of the following (Cl) to (C31); (Cl) halogen, (C2) lower alkyl, (C3) lower alkoxy, (C4) lower haloalkyl, (C5) lower haloalkoxy, (C6) lower alkenyl, (C7) lower alkylcarbamoyl, carbamoyl, phenyl lower alkylcarbamoyl, alkanoyl lower, (C8) lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, (C9) phenyl, naphthyl, (CIO) halophenyl, (Cll) hydroxyl, (C12) mono- or dihydroxyalkyl (lower), phenoxycarbonyloxy (lower) alkyl, (C13) amino), (C14) carboxyl, (C15) lower alkylenedioxy, (C16) lower alkanoylamino, phenylalkanoylamino (lower), halophenylalkanoylamino (lower), lower alkoxy-alkanoylamino (lower), lower alkoxy-alkanoylamino (lower), phenoxyalkanoylamino (lower), alkoxy-phenoxy lower alkanoylamino (lower), lower alkylphenoxy lower alkanoylamino, halophenoxy alkanoylamino (lower), carboxyalkanoylamino (lower), lower alkoxycarbonyl alkanoylamino (lower), lower alkylcarbamoyl alkanoylamino no (lower), haloalkanoylamino (lower), lower alkenyl alkanoylamino (lower), lower alkoxy alkanoylamino (lower), phenylalkoxy (lower) alkanoylamino (lower), p ip eridini 1 ox ia 1 c ano i 1 ami no (inferior), N-alkoxycarbonylpiperidinyloxy lower alkanoylamino (lower), pyridyloxyalkanoylamino (lower), hydroxyalkanoylamino (lower), lower alkanoyloxy alkanoylamino (lower), alkylcarbamoyloxy lower alkanoylamino (lower), N, N-di (lower alkyl) carbamoyloxy, piper i dinocarboni 1 ox ia 1-amino-1-amino (lower), phenylalkyl-carbamoyloxy (lower) alkanoylamino (lower), lower alkoxycarbonylamino-alkanoylamino (lower), aminoalkanoylamino (lower), lower alkoxycarbonylamino-alkanoylamino (lower), fluorenylmethoxycarbonylaminoalkanoylanum (lower), to the lower alkanoylamino ( lower), [N, N-di (lower alkyl) animo] alkanoylamino (lower), [N-lower alkyl-N- ( lower alkoxycarbonyl) animo] alkanoylamino (lower), [N-lower alkyl-N- (fluorenyl ethoxycarbonyl) to ino] alkanoylamino (lower), [N-alkyl mfepor-N- (mono- or dialkylcarbamoyl (lower)) animo] alkanoylamo (lower), [N- (mono- or di (lower alkyl) ca rb master 11) ammo] alkanoylamm (lower), benzoylammoalkanoylamino (lower), lower alkanoylamm alkanoylamm (lower), lower alkylsulfonylamine alkanoylamino (lower), lower alkoxy alkanoylamino (lower) alkanoylamm (lower), cycloalkyloxycarbonylamm (lower) alkanoylamm (lower), pyridylcarbonylamm alkanoylamm (lower), morph 1 mochaboni 1 ammoal cannibal (lower), phenylalkoxycarbonylamm (lower) alkanoylamm (lower), alkoxyphenylsulfonylamm lower alkanoylamm (lower) ), lower hydroxyalkylamine, alkanoylamine (lower), morpholmoalkanoylamine (lower), oxooxazolidinilalcanoylamm (lower), oxopyrrolidilnilalcanoilammo (lower), trimethylhydantoinyl canoilanu.no (lower), alkenylamino lower alkanoylamino (lower), lower alkoxy lower alkylammo) alkanoylamm (lower), phenylalkylamino (lower) alkanoylamm (lower), pyridylalkylammo (lower) alkanoylamm (lower), lower alkoxycarbonylammo, phenylalkoxycarbonylamino ( lower) lower alkoxy alkoxycarbonylamm (lower), haloalkoxycarbonylamine (lower), ammoalkoxycarbonylamine (lower), phthalimidoalkoxycarbonylamine (lower), carbamoylamino, (mono- or dialkyl lower) carbamoylamino, naphthylcarbamoylamo, halophenylcarbamoylammo, lower alkoxyphenylcarbamoylammo, lower alkenylcarbamoylamino, lower alkylaminocarbamoylamino (lower) cycloalkyl, phenylalkylcarbamoylamino (lower), haloalkylcarbamoylamm (lower), lower alkoxy alkylcarbamoylamm (lower), hydroxyalkylcarbamoylamino (lower), (lower alkyl) (diphenyl) silyloxyalkyl carbamoylamino (lower), carboxyalkylcarbamoylamino (lower), lower alkoxycarbonyl alkylcarbamoylamino (Lower) alky Icarbamoil alquilcarbamoilamino lower (inferior) or piridilcarbamoilaitu.no, lower alquilsulfonilammo, lower alquenoilammo, lower cicloalcancarbonilamino, lower alqueniloxicarbonilammo, phenoxycarbonylamino, lower alquiltiocarbonilammo, (C17) phenyl (lower), (C18) lower alkenyl, mono- or di (lower alkyl) carbamoylalkenyl (lower), (2- (methylcarbamoyl) ethenyl, 2- (ethylcarbamoyl) ethenyl, 2- (propylcarbamoyl) ethenyl, 2 - (isopropyl 1 carbamo 11) et eni 1, 2- ( dimethylcarbamoyl) ethenyl, enilcarbarmoilalquenilo f (lower) alcoxicarba lower oil (lower) alkenyl, halofenilcarbamoilalquenilo (bottom), (C19) alkylaminocarbonyloxy lower, (C20) lower alkanoyloxy, (C21) alkoxy lower alkanoyloxy (lower), (C22) lower alkoxycarbonyloxy , (C23) pyridylalkenoyloxy (lower), (C24) lower cycloalkanecarbonyloxy, (C25) carboxyalkoxy (lower), lower alkoxycarbonyl lower alkoxy, lower lower noil (lower) alkoxy, lower cicloalcancarbamoil (lower) alkoxy, lower alkylcarbamoyl lower alkoxy, (C26) alquilocarbamoiloxi lower (lower) alkyl, (C27) lower alkoxycarbonylamino alkyl (lower), (C28) alkylamino (lower), (C29) lower alkylcarbamoyl (lower) alkyl, (C30) furylcarbonylamino, teretahydroisoquinolyl-carbonylamino, N- a 1 cox i c a rboni 1 or lower-teretahydroisoquinolylcarbonylamino, pyrrolidinylcarbonylamino, (C31) oxazolyl, lower alkyloxanediazolyl. (V) The compounds (I) indicated in subsection (iv), in which a group of the formula: e the following formulas R2 is a hydroxyaminocarbonyl, m is 0 and n is 1, a group of the formula: Rl. -or is one of the group of the following formulas: (a) a Rll v W where R1 is a halo (for example bromine, etc.), naphthyl (for example 2-naphthyl, etc.), phenyl (for example phenyl etc.), mono- or dihalophenyl (for example 3 ( or 4) -chlorophenyl, 2 (or 3 or 4) -fluorophenyl, 3,4-d? chlorophenol, 3,5-d? fluorophenyl, etc.), mono- or dialkylphenyl (lower) (eg 3 ( or 4) -methylphenyl, 4-ethylphenyl, 4-? -propylphenyl, 4- (t-butyl) phenyl, 3,4-d? -methyl, etc.), lower alkoxyphenyl (e.g. -metox? phen? I, 4-ethoxyphenyl, etc.), trihaloalquilfenilo (lower) alkyl (for example 4-trifluorometilfemlo, etc.), tphaloalcoxifenilo (lower) alkyl (for example 4-tpfluormetox? phen? I, etc.), alkenylphenyl lower (e.g. 4-ethen? lphene, etc.), lower alkylcarbamoylphenyl (e.g. 4-methylcarbamoyl-4-ethylcarbamoyl, etc.), carbamoylphenyl (for example 4- carbamolefin, etc.), phenylalkylcarbamoylphenyl (lower) (for example 4-benzylcarbamoylphenyl, etc.), lower alkanoylphenyl (for example 4-acetylphenol, etc.), alkythiophenyl , lower alquilsulfinilfenilo, lower alkylsulfonylphenyl (for example 4-methylthiophenyl, 4-et? lt? ofen? I, 4-meth? lsulf? n? lfen? I, 4-methylsulfonylphenyl, etc.), phenylphenyl (e.g. phenylphenyl etc.), (halo) (phenyl) phenyl (e.g. 4-phenol-3-fluorophenol etc.), halophenylphenyl (e.g. 4- (4-fluorophenyl) phenyl etc.), hydroxyphenyl (e.g. (or 4) hydroxyphenyl, etc.), mono- or dihidroxialquilfenilo (lower) alkylphenyl phenoxycarbonyloxy (lower) (eg 3 (or 4) -hidroximetilfenilo, 4- (1,2-dihydroxyethyl) phenyl4- (phenoxycarbonyloxymethyl) phenyl, etc.), aminophenyl (for example 3 (or 4) -aminophenyl, etc.), carboxyphenyl (for example 4-carboxyphenyl, etc.), lower alkylenedioxyphenyl (for example 3,4-methylenedioxyphenyl) , etc.), lower alkanesulphonylaminophenyl (for example 4- (methanesulfonylamino) phenyl etc.), lower alkenylaminophenyl, (for example 3- (2-butenoynyl) phenyl, etc.), cycloalkanecarbonylaminophenyl lower (for example 3- (cyclopropanecarbonylamino) phenyl, 3- (cyclobutanecarbonylamino) phenyl, 3- (cyclopentanecarbonylamino) phenyl, etc.) phenylalkoxyphenyl (lower) (for example 4-benzyloxyphenyl, etc.), carbamoylalkenylphenyl (lower), mono- or di (lower alkyl) carbamoylalkenylphenyl (lower ) (for example 4- (2- (methylcarbamoyl) ethenyl) phenyl, 4- (2- (ethylcarbamoyl) ethenyl) phenyl, 4- (2- (propylcarbamoyl) ethenyl) phenyl, 4- (2- (isopropicarbamoyl) ethenyl) phenyl, 4-2- (dimethylcarbamoyl) ethenyl) phenyl, etc.) phenylcarbamoylalkenyl (lower) (e.g. - (2- (phenylcarbamoyl) ethenyl) phenyl, etc.), alkoxycarbamoyl lower alkenyl (lower) (for example 4- (2-methoxyphenylcarbamoyl) ethenyl) phenyl, etc.), halophenylcarbamoylalkenyl (lower) (for example 4- (2 4-fluorophenylcarbamoyl) ethenyl) phenyl, etc.), lower alkylcarbamoyloxyphenyl (for example 4- (methylaminocarbonyloxy) phenyl, 4- (ethylaminocarbonyloxy) phenyl, etc.), lower alkanoyloxyphenyl (for example 4-propanoyloxyphenyl, etc.) lower alkoxy alkanoyloxyphenyl (lower) (for example 4- (methoxyacetyloxy) phenyl, etc.), lower alkoxycarbonylsiloxyphenyl (for example 4- (ethoxycarbonyloxy) phenyl, etc.), pipdilalkenoiloxifem (lower) for example 4- (3- (3-p? r? d? l) acryloyloxy) phenyl, etc. ), cycloalkylcarbomloxifem (lower) (for example 4- (cyclopropylcarbonyloxy) phenyl, etc.), carboxyalkoxyphenyl (lower) (for example 4- (carboxymethoxy) phenyl, etc.) alkoxycarbonyl lower alkoxyphenyl (lower) (for example 4- (ethoxycarbonylmethoxy) ) phenyl, 4- (t-butoxycarbonylmethoxy) phenyl, etc.), lower alkoxy lower alkoxyphenyl (for example 4- (propanoylmethoxy) phenyl, etc.), cycloalkancarbamoyl lower alkoxyphenyl (lower) (for example 4- (cyclopropylcarbamoylmethoxy) phenyl, etc.), alkylcarbarmoyl lower alkoxyphenyl (lower) (for example 4- (methylcarbamoylmethoxy) phenyl, 4- (ethylcarbamoylmethoxy) phenyl, 4- (propylcarbamoylmethoxy) phenyl, etc.), alkylcarbamoyloxy lower alkylphenyl (lower) (for example (or 4) - (methylcarbamoyloxymethyl) phenyl, etc.), alkoxycarbonylamino lower alkylphenyl (for example 4- (methoxycarbonylaminomethyl) phenyl, 4- (t-butoxycarbonylaminomethyl) phenyl, etc.) aminoalkylphenyl (lower) (for example 4) -am? no methanol, etc.), alkylcarbamoyl lower alkylphenyl (lower) (e.g. 4- (methylcarbamoylmethyl) phenyl, etc.), furylcarbonylaminophenyl, 1,2,3, 4-teretah? d? so? -nol i lcarboni lamino fem lo, N-Boc- 1, 2, 3, 4 - t er et a-hydroisoquinolilcarbonylaminophenyl, pyrrolidinylcarbonylazo.nofenil (for example 3- (2 (or 3) -fuplcarbonylamino) phenyl, 3- (1,2, 3,4-teretahydroisoquinolylcarbonylamino) phenyl, 3- (N- (t-butoxycarbonyl) -1,2,3, 4- tereta? dro? soqumol? lcarbon? lammo) phenyl, 3- (pyrrolidinylcarbonylamino) phenyl, etc.), oxazolylphenyl (for example 4- (1, 3-oxazole?) phenyl, etc.), alkyloxadiazolylphenyl, (for example - (5-met? Ll, 2, 4-oxad? Azol-3-? Lo) phenyl, etc.), wherein R 12 is lower alkyl (for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, neopentyl, etc.) optionally substituted by the group consisting of phenyl (for example phenyl, etc.), halophenyl ( for example 4-chlorophenyl, etc.), lower alkoxyphenyl (for example 4-methoxyphenyl, etc.), lower alkoxy (for example methoxy, ethoxy, propoxy, butoxy, isopropyloxy, etc.), phenoxy (for example phenoxy, etc.), lower alkoxyphenoxy (for example 3 (or 4) -methoxyphenoxy, etc.), halofenoxy (for example 4-fluoro (or chloro) phenoxy, etc.), lower alkylphenoxy (for example 3 (or 4) -methylphenoxy) , etc.), carboxy (for example carboxy, etc.), lower alkoxycarbonyl (for example methoxycarbonyl, t-butoxycarbonyl, etc.), lower alkylcarbamoyl (for example methylcarbamoyl, etc.), halo (for example chlorine, etc.) , lower alkenyloxy (for example allyloxy etc.), lower alkoxy lower alkoxy (for example 2-ethoxy? ethoxy ?, etc.), phenylalkoxy (lower) (for example benzyloxy) , etc.), piperidyloxy (for example 4-p? pepd? n? lox ?, etc.), Nt-butoxycarbonylpiperidyloxy (for example Nt-butox? carbon? l-4-p? per? d? mlox ?, etc .) pyridyloxy (for example 3 (or 4) -piplyloxy, etc.), hydroxy (for example hydroxy, etc.), lower alkanoyloxy (for example acetoxy etc.), mono- or dialkylcarbamoyloxy (lower) (for example methylcarbamoyloxy, N-methyl-N-ethylcarbamoyloxy, etc.), piperidimlcarbonyloxy (for example piperidmcarbonyloxy, etc.), phenyl alkylcarbamoyloxy (lower) (for example benzylcarbamoyloxy, etc.), lower alkoxycarbonylamino (for example methoxycarbonylamm, ethoxycarbonylamm, propoxycarbonylamm, t-butoxycarbonylamm, etc.), ammo (for example, one, etc.), lower alkoxycarbonylamine (for example methoxycarbonylamine, t-butoxycarbonylamino, etc.), fluorenylmethoxycarbonylamine (for example fluorenylmethoxycarbonylamino etc.), mono- or dialkylamino (lower) (for example methylamine, ethylamino, dimethylamine, N) -methyl-N-ethylamino, t-butylamine, pentylamine etc.), N-lower alkyl N- (lower alkoxycarbonyl) amino (for example N-methyl-N-methoxycarbonylamine, N-methyl-N-t-butoxycarbonylammo-N-ethyl-N-t-butoxycarbonyl am m, e t c. ), N- to the lower N- (fluorenyl ethoxycarbonyl) ammo (for example N-methyl-N- (fluorenylmethoxycarbonyl) ammo etc.), N-lower alkyl N- (mono- or dialkylcarbamoyl) (lower) to one (per example N-methyl-N- (dimethylcarbamoyl) ammo, etc.), N- (mono- or di (lower alkyl) carbamoyl) amino (for example dimethylcarbamoyl-N-methylcarbamoyl) amino, etc.), benzoylamine (for example benzoylamine) , etc.), lower alkanoyl ammonium (eg acetylamm, isobutylamm, pivaloyl ammon, etc.), lower alkanesulphonylamine (eg methanesulfonylamine, etc.), lower alkoxy alkanoylamm (lower) (eg methoxyacetylamm, etc.), cycloalkyloxycarbonylamine (lower) (eg cyclopentyloxycarbonylamm, etc.), pipdilcarbonylamm (for example pyridylcarbonylamm, etc.), mor fol incarboni 1 amino (eg morpholinecarbonylamm, etc.), phenylalkoxycarbonylamm (lower) (eg benzyloxycarbonylamine, etc.), lower alkoxyphenylsulfonylamine (for example 4-methoxyphenylsulfonylamine, etc.), hydroxyalkylamine (lower) (for example 2-hydroxy ethanol, etc.), morphol (for example morphol, etc.) oxooxazolidinyl (for example 2-oxo-l, 3-oxazole? dm-l-1o, etc.), oxopyrrolidinyl (eg 2-oxoprolitro dm-l-α, etc.), tpmethylhydantomyl (e.g. 3, 4, 4-tr? met? lh? dantom-l-yl, etc.). ), pyridyl (for example 3 (or 4) -p? r? d? lo, etc.), lower alkenylamm (for example allylamine, etc.), lower alkoxy lower alkylamine (for example 2-ethoxyethylamino, etc.). ), phenylalkylamino (lower) (for example benzylamino, etc.), pyridylalkylamino (lower) (for example 3-pyridylmethylamino, etc.) and cyclo (lower) cyclohexyl, etc.), wherein M is oxygen or sulfur, R 13 is a lower alkyl (for example methyl, ethyl, propyl, isopropyl, etc.), phenylalkyl (lower) (for example benzyl, etc.), lower alkoxy (lower) alkyl (for example 2-methoxyethyl, etc.), haloalkyl (lower) (for example 2-chloroethyl, etc.), aminoalkyl (lower), phthalimidoalkoxycarbonylamino (lower) (for example 2-aminoethyl, 2-phthalimidoethyl, etc.), lower alkenyl ( for example allyl, etc.), phenyl (for example phenyl, etc.), wherein R15 is hydrogen, or lower alkyl (e.g. methyl, etc.), R14 is hydrogen, lower alkyl (e.g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, etc.), naphthyl (eg example 1-naphthyl, etc.), halophenyl (for example 3 (or 4) -chlorophenyl, etc.), lower alkoxyphenyl (for example 4-methoxyphenyl, etc.), lower alkenyl (for example allyl, etc.), cycloalkyl (lower) alkyl (lower) (for example cyclohexylmethyl, etc.), phenylalkyl (lower) (for example benzyl, etc.), haloalkyl (lower) (for example 2-chloroethyl, etc.), lower alkoxy (lower) alkyl (for example methoxymethyl, 2-methoxyethyl, etc.), hydroxyalkyl (lower) (for example 2-hydroxyethyl, etc.), (lower alkyl) (diphenyl) silyloxyalkyl (lower) (for example 2- ((t-butyl)) (diphenyl) silyloxy) ethyl, etc.), carboxyalkyl (lower) (for example carboxymethyl, etc.), lower alkoxycarbonyl (lower) alkyl (for example ethoxycarbonylmethyl, etc.) , lower alkylcarbamoyl (lower) alkyl (for example methylcarbamoylmethyl, etc.), or pyridyl (for example 3-pyridyl, etc.), wherein R16 is benzothienyl (for example 2-benzothienyl, etc.), benzofuranyl (for example 2-benzofuranyl, etc.), thienyl (for example 2 (or 3) -thienyl, etc.), furyl (for example 2- furyl, etc.), pyridyl (e.g. 3-pyridyl, etc.), lower alkylpyridyl (e.g. l-methyl-4-pyridyl, 6-methyl-3-pyridyl, etc.), lower alkoxypyridyl (e.g. methoxy-3-pyridyl, etc.), lower alkoxycarbonylaminopyridyl (e.g. 5-methoxycarbonylamino-3-pyridyl, etc.), lower alkanoylthienyl (e.g. 5-acetyl-2-thienyl, etc.), lower alkylcarbamoylbenzofuranyl (e.g. -methylcarbamoyl-5-benzofuranyl, etc.). (vi) The compounds (I) of part (v), where a group of the formula: Rl. OR" is the same group as (a), (c), (d) and (e) of claim 7, and the following formula (b): wherein R 12 is lower alkyl, phenylalkyl (lower), halophenylalkyl (lower), lower alkoxyphenyl lower alkyl, lower alkoxy lower alkyl, phenoxyalkyl (lower), lower alkoxyphenoxy lower alkyl, halophenyl (lower) alkyl, lower alkylphenoxy alkyl ( lower), carboxyalkyl (lower) alkoxycarbonyl lower (lower) alkyl, lower alkylcarbamoyl (lower) alkyl, haloalkyl (lower), lower alkenyloxy (lower) alkyl, lower alkoxy (alkoxy) (lower) alkyl (lower), phenylalkoxy (lower) alkyl (lower), piperidinyloxyalkyl (lower), Nt-but oxyi carboni lpiper idyloxial which (lower), pyridyloxyalkyl (lower), hydroxyalkyl (lower), alkanoyloxy lower alkyl (lower) ), mono- or dialkylcarbamoyloxy (lower) alkyl (lower), piperidinylcarbonyloxyalkyl (lower), phenylalkylcarbamoyloxy (lower) alkyl (lower), lower alkoxycarbonylamino (lower) alkyl, aminoalkyl (lower), lower alkoxycarbonylamino (lower) alkyl, fluornylmethoxycarbonylaminoalkyl (lower) ), mono- or dialkylamino (lower) alkyl (lower), N-lower alkyl N- (lower alkoxycarbonyl) aminoalkyl (lower), N-lower alkyl N- (fluornylmethoxycarbonyl) aminoalkyl (lower), N-lower alkyl N- ( mono- odi (a 1 qu i 1 ca rb amo i 1) (lower) aminoalkyl (lower), N- (mono- or di (lower alkyl) carbamoyl) aminoalkyl (lower), benzoyl-inoalkyl (lower) alk lower alkylamino lower alkyl, lower alkylsulfonylamino lower alkyl, lower alkoxy alkanoylamino (lower) alkyl (lower), cycloalkyloxycarbonylamino (lower) alkyl (lower), pyridylcarbonylaminoalkyl (lower), morpholincarbonylaminoalkyl (lower), phenylalkoxycarbonylamino (lower) alkyl ( lower), lower alkoxyphenylsulfonylamino lower alkyl lower hydroxyalkylamino lower alkyl lower alkyl, morpholinal lower alkyl, oxooxazolidinyl lower alkyl (lower) oxopyrrol idini lalqui lo (lower), trimethylhydantoinylalkyl (lower), pyridylalkyl (lower), lower alkenylamino lower alkyl lower alkylamino (lower) alkyl (lower), phenylalkylamino (lower) alkyl (lower), pyridylalkylamino (lower) alkyl (lower), cycloalkyl (lower), (amino) (phenyl) alkyl (lower) (for example 2-f eni 1-1-aminoe ti lo, etc.), (lower alkoxycarbonylamino) (phenyl) alkyl (lower) (for example 1-amino-1-phenylmethyl, 1-t-butoxycarbonylamino-1-phenylmethyl) , l-amino-2-phenylethyl, 1-t-butoxycarbonylamino-2-phenylethyl, etc.), (amino) (lower alkoxy) lower alkyl (for example l-amino-2-methoxyethyl, etc.), ( lower alkoxycarbonylamino) - (lower alkoxy) lower alkyl (for example lt-butoxycarbonylamino-2-methoxyethyl, etc.), (amino) (carboxy) alkyl (lower), (lower alkoxycarbonylamino) (carboxy) alkyl (lower) ), (amino) (lower alkoxycarbonyl) alkyl (lower), (lower alkoxycarbonylamino) (lower alkoxycarbonyl) -alkyl (lower) (for example l-amino-3-carboxypropyl, 1-t-butoxycarbonylamino-3-carboxypropyl, l-amino-3- (t-butoxycarbonyl) propyl, lt-butoxycarbonylamino -3-t-butoxycarbonylpropyl, etc.) (amino) (phenylalkoxy lower) alkyl (lower), (lower alkoxycarbonylamino) (lower phenylalkoxy) lower alkyl (for example 1-amino-2-benzyloxyethyl, l-t-butoxycarbonylamino-2-benzyloxyaminoethyl, etc.), (amino) (pyridyl) alkyl (lower), (lower alkoxycarbonylamino) (pyridyl) lower alkyl (for example l-amino-2- (3-pyridyl) ethyl, 1-t-butoxycarbonylamino-2- (3-pyridyl) ethyl, l-amino- 2- (4-pyridyl) ethyl, lt-butoxycarbonylamino-2- (4-pyridyl) ethyl, etc.), (amino) (hi dr ox i) at 1 qu i 1 (lower), (lower alkoxycarbonylamino) (hydroxy) lower alkyl (for example 1-amino-2-hydroxyethyl, 1-t-butoxycarbonylamino-2-hydroxyethyl, etc.), (amino) (amino) (lower) alkyl, (lower alkoxycarbonylamino) (amino) lower alkyl, (amino) lower alkoxycarbonylamino) lower alkyl, lower alkoxycarbonylamino) lower alkoxycarbonylamino lower alkyl (for example 1, 5-diaminopentyl, 1-t-butoxycarbonylamino-5-aminopentyl, 1,5-bis (t-butoxycarbonylamino) pentyl, l-amino-5- (t-butoxycarbonylamino) pentyl, etc.), (amino) (lower cycloalkane) alkyl (lower), alkoxycarbonylamino (lower) (lower cycloalkane) lower alkyl (for example 1-amino-2-cyclohexylethyl, 1-t-butoxycarbonyl-lamino-2-cyclohexylethyl, etc.). vii) The compounds (I) indicated in subsection (vi) where a group of the formula: Rl. -H.H" is the group of the following formula (a) where R11 is bromine, 2-naphthyl, phenyl, 3 (or 4) -chlorophenyl, 2 (or 3 or 4) -fluorophenyl, 3,4-dichlorophenyl, 3,5-difluorophenyl, 3 (or 4) -methylphenyl, 4- ethylphenyl, 4-isopropylphenyl, 4- (t-butyl) phenyl, 3,4-dimethylphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-trifluoromethylphenyl, 4-trifluoromethoxyphenyl, 4-ethenylphenyl, 4-methylcarbamoylphenyl, 4-ethylcarbamoylphenyl, -carbamoylphenyl, 4-benzylcarbamoylphenyl, 4-acetylphenyl, 4-methylthiophenyl, 4-ethylthiophenyl, 4-methylsulfinylphenyl, 4-methylsulfonylphenyl, phenylphenyl, 4-phenyl-3-fluorophenyl, 4- (4-f luorofenyl) phenyl, 3 ( or 4) -hydroxyphenyl, 3 (or 4) -hydroxymethylfluoryl, 4- (1,2-dihydroxyethyl) phenyl, 4- (phenoxycarbonyloxymethyl) phenyl, 3 (or 4) -aminophenyl, 4-carboxyphenyl, 3,4-methylenedioxyphenyl 4- (methanesulfonylamino) phenyl, 3- (2-butanoylamino) phenyl, 3- (cyclopropanecarbonylamino) phenyl, 3- (cyclobutanecarbonyl-amino) phenyl, 3- (cyclopentanecarbonylamino) phenyl, 4-benzyloxyphenyl, 4- (2- ( methylcarbamoyl) ethenyl) phenyl, 4- (2- (ethyl carbamoyl) ethenyl) phenyl, 4- (2 (propylcarbamoyl) ethenyl) phenyl, 4- (2- (isopropylcarbamoyl) ethenyl) phenyl, 4-2- (dimethylcarbamoyl) ethenyl) phenyl, 4- (2- (phenyl Icarbamoyl) ethenyl) phenyl, 4- (2- (methoxyifenylcarbamoyl) ethenyl) phenyl, - (2- (4-fluorophenylcarbamoyl) ethenyl) phenyl, 4- (methylaminocarbonyloxy) phenyl, 4- (ethylaminocarbonyloxy) phenyl, 4-propanoyloxyphenyl, 4- (methoxyacetyloxy) phenyl, 4- (ethoxycarbonyloxy) phenyl, 4- (3- (3-pyridyl) acryloyloxy) phenyl, 4- (cyclopropylcarbonyloxy) phenyl, 4- (carboxymethoxy) phenyl, 4- (ethoxycarbonylmethoxy) phenyl, 4- (t-butoxycarbonylmethoxy) phenyl, 4- (propanoylmethoxy) phenyl, - (cyclopropylcarbamoylmethoxy) f enyl, 3 (or 4) - (methylcarbamoylmethoxy) phenyl, 4- (ethylcarbamoylmethoxy) phenyl, 4- (propylcarbamoylmethoxy) phenyl, 3 (or 4) - (methylcarba oyloxymethyl) phenyl, 4- (methoxycarbonylamino-methyl) phenyl, 4- (t-butoxycarbonylaminomethyl) phenyl, 4-aminomethyl phenyl, 4- (methylcarbamoylmethyl) phenyl, - (2 (or 3) 'furylcarbonylamino) phenyl, 3- (1, 2, 3, 4-teretahydroisoquinolylcarbonylamino) phenyl, 3- (N- (t-butoxycarbonyl) -1, 2, 3, 4-teretahydroisoquinolylcarbonyl-amino) phenyl, 3- (pyrrolidinylcarbonylamino) phenyl, 4- (1,3-oxazolyl) phenyl, 4- (5-methyl-1,2,4-oxadiazol-3-yl) phenyl, wherein R12 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, neopentyl, f-enylmethyl, 4-chlorofenylmethyl, 4-metoxif in 1-methyl, methoxymethyl, ethoxymethyl, pr opo x ime ti 1 o, bu t ox ime ti 1 o, i sopr op i 1 ox ime ti 1 o, 1 -me t ox ieti 1 o, 2 -me toxieti 1 o, phenoxymethyl, 2-phenoxyethyl, 3 (o 4) -me t ox if eno x ime ti 1 or, 4-fluoro (or chloro) phenoxymethyl, 3 (or 4) -methylf enoxymethyl, 2-carboxyethyl, 2 -me toxy carboni 1 et i lo, 2-t -bu t oxo arbon i 1 eti 1 o, 2-methylcarbamoylethyl, 2-chloroether, chloromethyl, allyloxymethyl, (2-etox? Etox?) Methyl, benzyloxymethyl, 4-p? Per? D? N? Lox? Met? Lo, (N-t-butox? Carbon? L-4-p? Per? D? N?) Oxymethyl, 3 (or 4) -pipdhyloxymethyl, hydroxymethyl, 2-hydroxyl, acetoxymethyl, 1-acetoxyethanol, methylcarbamoyloxymethyl, 1- (N-methyl-N-ethylcarbamoyloxy) methyl, (piperidmocarbonyloxy) methyl, (benzylcarbamoyloxy) methyl, (t-butoxycarbonylamm) methyl, ammomethyl, 1-ammoetyl, 1- (t-butoxycarbonylamm) ethyl, 2-ammoethyl, methoxycarbonylaminomethyl, 2- (methoxycarbonylamm) ethyl, ethoxycarbonylamomethyl, propoxycarbonylamomethyl, 1- (fluoronylmethoxycarbonylamino ) methyl, 2- (t-butoxycarbonylammo) ethyl, 2- (fluorenylmethoxycarbonylamino) ethyl, 1-ammonopropyl, 1-ammopropyl, 1- (t-butoxycarbonylammo) propyl, 1- (t-butoxycarbonylammo) isopropyl, 1,5-d? Ammopentyl, l, 5-b? S (t-butox? Carbon? Lammo) pentyl, methylaminomethyl, ethylamomethyl, 3- (2- (N-methyl-N-ethylan) methyl, 3- (dimethylamomethyl), 3- (penti lammomethyl), 3- (t-buty lammomethyl), 3- (3-methylamomethyl), 3- ( 2- (N-met? LN-methox? Carbon? Lam? No) met? Lo, 1- (N-met? LNt-butox? Carbon? Lammo) met? Lo, 1- (N-ethyl-Nt-butoxycarbonilam) ) methyl, 2- (N-ethyl-N- (fluorenylmethoxycarbonyl) ammo) ethyl, 2- (N-methyl-N- (t-butoxycarbonyl) ammo) ethyl, 1- (N-methyl-N- (dimethylcarbamoyl) animo ) methyl, 1- (dimethylcarbamoylamino) methyl, 1- (N- (eti Icarbamoyl) ammo) methyl, 2- (N- (ethylcarbamoyl) ermine) ethyl, benzoylammomethyl, 2-benzo-lammoetyl, acetylamine omethyl, isobutyryl-omethyl , pivaloylaminomethyl, 1- (methanesulfonylamino) methyl, 2- (methanesulfonylamino) ethyl, methoxyacetylaminomethyl, cyclopentyloxycarbonylaminomethyl, pyridicarboni laminomethyl, mor folinocarboni laminomethyl, benzyloxycarbonylaminomethyl, 1- (4-methoxyphenylsulfonylamino) methyl, 1- (2- hydroxyethylamino) methyl, morpholinmethyl, 1- (2-oxo-1,3-oxazotidin-1-yl) methyl, 1- (2-oxophoxy) irrolidin-l-yl) methyl, 1- (3,4-trimethylhydantoin-1-yl) methyl, allylaminomethyl, 1- (2-ethoxyethylamino) methyl, benzylaminomethyl, 1- (3-pyridylmethylamino) methyl, 2-phenyl -l-aminoethyl, 1-amino-1-phenylmethyl, 1-t-butoxycarbonylamino-1-p-enylmethyl, l-amino-2-p-phenylethyl, 1-t-butoxycarbonylamino-2-phenylethyl, l-amino-2-methoxyethyl , 1-t-butoxycarbonylamino-2-methoxyethyl, l-amino-3-carboxypropyl, t-butoxycarbonylamino-3-carboxypropyl, l-amino-3- (t-butoxycarbonyl) propyl, 1-t-butyloxycarbonyl amino-3 -t-butoxycarbonylpropyl, etc.), l-amino-2-benzyloxyethyl, 1-t-butoxycarbonylamino-2-benzyloxyaminoethyl, l-amino-2- (3-pyridyl) ethyl, lt-butoxycarbonylamino-2- (3-pyridyl) ) ethyl, 1-amino-2- (4-pyridyl) ethyl, lt-butoxycarbonylamino-2- (4-pyridyl) ethyl, l-amino-2-hydroxyethyl, lt-butoxycarbonylamino-2-hydroxyethyl, (1, 5) diaminopentyl, lt-butoxycarbonylamino-5-aminopentyl, 1,5-bis (t-butoxycarbonylamino) pentyl, l-amino-5- (t-but oxycarbonyl lamino) pentyl, l-amino-2-cyclic ohexylethyl, 1-t-butoxycarbonylamino-2-cyclohexylethyl, wherein M = 0 and R13 is a methyl, ethyl, propyl, isopropyl, benzyl, 2-methoxyethyl, 2-chloroethyl, 2-aminoethyl, 2-phthalimidoethyl, allyl, phenyl, or M = S and R13 is methyl, ethyl, wherein R15 is hydrogen and R14 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, 1-naphthyl, 3 (or 4) -chlorophenyl, 3-methoxyphenyl, allyl, cyclohexylmethyl, benzyl, 2- chloroethyl, methoxymethyl, 2-methoxyethyl, 2-hydroxyethyl, 2- ((t-butyl) (diphenyl) silyloxy) ethyl, carboxymethyl, ethoxycarbonylmethyl, methylcarbamoylmethyl, or 3-pyridyl, R14 is ethyl and R15 is methyl, wherein Rld is 2-benzothienyl, 2-benzofuranyl, 2 (or 3) -thienyl, 2-furyl, 3-pyridyl, l-methyl-4-pyridyl, 6-methyl-3-pyridyl, 6-methoxy-3 pyridyl, 5-methoxycarbonylamino-3-ITC pyridyl, 5-acetyl-2-thienyl, 2-methylcarbarmoyl-5-benzofuranyl. The processes for preparing the subject compounds are explained in detail below. Process 1 The object compound (I-b) or a salt thereof can be prepared by subjecting a compound (I-a) or a salt thereof to the removal reaction of the protective carboxyl group. Suitable salts of the compounds (I-a) and 0 (I-b) refer to those exemplified for the compound (I) This reaction is carried out according to a conventional method such as solvolysis, including hydrolysis, reduction or the like. The solvolysis is preferably carried out in the presence of a base or an acid, which includes a Lewis acid. A convenient base may include an inorganic base and an organic base such as an alkali metal (eg, sodium, lithium, potassium), an alkaline earth metal (eg, magnesium, calcium, etc.), its hydroxide, carbonate or bicarbonate, hydrazide, trialkylamma (for example trimethylamine, triethylamine, etc.), picolma, 1,5-d? azab? c? clo [4.3. or] -non-5-ene, 1,4-diazabicyclo [2.2.2] octane, 1,8-d? azab? c? clo [5.4.0] undec-7-ene, or the like. A suitable acid may include an organic acid (eg formic acid, acetic acid, propionic acid, trichloroacetic acid, tpfluoroacetic acid, etc.), an inorganic acid (eg hydrochloric acid, hydrobromic acid, sulfuric acid, hydrogen chloride, bromide of hydrogen, hydrogen fluoride, boron trifluoride diethyl etherolite, hydrogen iodide, etc.). The removal reaction with an acid such as trihaloacetic acid (for example trichloroacetic acid, tpfluoroacetic acid, etc.) or the like is preferably carried out in the presence of cation sequestering agents (for example anisole, phenol, etc.). .). In general, the reaction occurs in a solvent such as water, an alcohol (for example methanol, ethanol, etc.), methylene chloride, chloroform, carbon tetrachloride, dioxane, tetrahydrofuran, N, N-dimethylformamide, a mixture of these or any other solvent that does not have a negative effect on the reaction. A liquid base or acid can also be used as a solvent. The temperature of the reaction is not a critical point and, in general, the reaction occurs at low to high temperatures. The reduction method applicable to the removal reaction may include chemical reduction and catalytic reduction. Among the reducing agents suitable for use in chemical reduction may include a combination of metal (eg tin, zinc iron, etc.) or a metal compound (eg, chromium chloride, chromium acetate, etc.) with an acid organic or inorganic (for example formic acid, acetic acid, propionic acid, trifluoroacetic acid, p-toluenesulfonic acid, hydrochloric acid, hydrobromic acid, etc.) Among the catalysts suitable for use in catalytic reduction are conventional catalysts such as platinum (eg platinum plate, platinum sponge, platinum black, colloid platinum, platinum oxide, metal platinum, etc.), palladium catalysts (eg palladium sponge, palladium black), palladium oxide, palladium on carbon, palladium colloid, palladium on barium sulfate, palladium on barium carbonate, etc.), nickel catalysts (for example nickel reduced, nickel oxide, nickel Ranei, etc.), cobalt catalysts (for example reduced cobalt, cobalt from Ranei, etc.), iron catalysts (for example reduced iron, Ranei iron, etc.), copper catalysts (for example reduced copper, Ranei copper, Ullman copper, etc.) and the like, and these catalysts can be used in combination with ammonium formate (for example a combination of palladium on carbon and ammonium formate, etc.). In general, the reduction is carried out in a conventional solvent that has no negative effect on the reaction, such as water, methanol, ethanol, propanol, N, N-dimethylformamide or a mixture thereof. In addition, in the aforementioned acids to be used in chemical reduction, were in liquid state, they can also be used as a solvent. Even, a convenient solvent used in the catalytic reduction may be the above-mentioned solvent, and conventional solvents such as diethyl ether, dioxane, tetrahydrofuran, etc., or a mixture thereof. The reaction temperature of this reduction is not a critical point and, in general, the reaction is carried out from low to high temperatures. Process 2 The compound (I-b) or a salt thereof can be prepared by oxidation of the compound (II) or a salt thereof. The appropriate salts of the compound (II) may be the same as those used for the compound (I). Oxidation is carried out in a conventional manner, which can cause oxidation of a vinyl group to a carboxyl group, and the appropriate oxidant reagent can be an oxy-acid such as periodate (eg, sodium periodate, potassium periodate, etc.). ), a peroxyacid such as perbenzoic acid (for example perbenzoic acid, m-chloroperbenzoic acid, etc.), OXONE (2KHS05.KHS04.K2S04), potassium permanganate, a combination of titanium (III) chloride with hydrogen peroxide, a combination thereof (for example a combination of potassium permanganate and sodium periodate, etc.), and the like . This reaction can be carried out in the presence of a suitable base, as mentioned above (for example potassium carbonate, etc.).

In general, the reaction is carried out in a conventional solvent such as water, alcohol (for example methanol, ethanol, isopropyl alcohol, t-butyl alcohol, etc.), tetrahydrofuran, dioxane, dichloromethane, ethylene dichloride, chloroform, N , N-dimethylformamide, N, N-dimethylacetamide, or another organic solvent that does not produce a negative effect on the reaction. Among these solvents, hydrophilic solvents mixed with water can be used. The reaction temperature is not a critical point and, in general, the reaction occurs at low to high temperatures. Process 3 The compound (I-d) or a salt thereof can be prepared by subjecting the compound (I-c) or a salt thereof to a reduction reaction. The appropriate salts of the compounds (I-c) and (I-d) may be the same as those used for the compound (I) • The reduction method applicable to this reaction can be the same as Process 1, which can convert a haloaryl group into an aplo group (for example a combination of palladium on carbon and ammonium formates, etc.). Process 4 The compound (Ie) or a salt thereof can be prepared by causing the reaction of the compound (Ib) or its reactive derivative in the carboxyl group, or a salt thereof with the compound (IV) or its reactive derivative in the group amino, or a salt thereof. Among the suitable reactive derivatives of the compound (IV) in the amino group is the Schiff base type imino or its tautomeric enamine type isomer formed by the reaction of the compound (IV) with a carbonyl compound such as aldehyde, ketone or the like; a silyl derivative formed by the reaction of the compound (IV) with a silyl compound such as bis (trimethylsilyl) acetamide, mono (trimethylsilyl) acetamide, bis (trimethylsilyl) urea, or the like; a derivative formed by the reaction of the compound (IV) with phosphorus trichloride or phosgene, and the like. Suitable salts of the compound (IV) and its reactive derivative can be referred to the acid addition salts as exemplified for the compound (I). Suitable salts for the compound (I-e) may be the same as those used for the compound (I). Convenient reactive derivatives of the compound (I-b) in the carboxy group may include a halide, an anhydride, an activated amide, an activated ester, and the like. Suitable examples of reactive derivatives may be an acid chloride, an acid azide, a mixed anhydride acid whose acid is a substituted phosphoric acid (for example dialkylphosphoric acid, phenylphosphoric acid, di-phenyl-phosphoric acid, dibenzylphosphoric acid, halogenated phosphoric acid, etc. ), dialkylphosphorous acid, sulfurous acid, thiosulfuric acid, sulfuric acid, sulphonic acid (for example methanesulfonic acid, etc.), aliphatic carboxylic acid (for example acetic acid, propionic acid, butyric acid, isobutyric acid, pivalic acid, pentanoic acid, isopentanoic acid, 2-ethyl-butyric acid, trichloroacetic acid, etc.) or aromatic carboxylic acid (for example benzoic acid, etc.); a symmetrical anhydride; an amide activated with imidazole, 4-substituted imidazole, dimethyl pyrazole, triazole or tetrazole; or an activated ester (for example cyanyl ester, methyl oxetane, dimethyl iminomethyl [(CH,) 2N + = CH-] ester, vinylester, propargyl ester, p-nitrophenylester, 2,4-dinitrophenyl ester, trichlorophenylester, pentachlorophenylester, mesylphenylester, phenylazophenylester, phenylthioster, p-nitrophenylthioester, p-cresylthioester, carboxy ethyl thioester, pyranylester, pyridylester, piperidyl esters, 8-quinolyl thioesters, etc.), or an ester with an N-hydroxy compound [e.g. N, N-dimethylhydroxylamine, l-hydroxy-2- (lH) -pyridone, N-hydroxysuccinimide, N-hydroxypheimide, 1-h? drox? -lH-benzotriazole, etc.], and the like. These reactive derivatives can optionally be selected from among them according to the type of compound (I-b) that is to be used. In general, the reaction is carried out in a conventional solvent such as water, alcohol [eg methanol, ethanol, etc.], acetone, dioxane, acetonitop, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, ethyl acetate , N, N-dimethyl ormamide, pyridine or any other organic solvent that does not produce a negative effect on the reaction. These conventional solvents can also be used mixed with water. In this reaction, when the compound (I-b) is used in some form free of acid or in the form of its salt, the reaction is preferably carried out in the presence of a conventional condensing agent such as N, N'-dicyclohexylcarbodumide; N-c? Clohex? L-N '-morphol ethylcarbodi-amide; N-c? Clohex? L-N '- (4-d? Et? Lam? Nc? Clohex? L) carbodirride; N, N'-diethylcarbodnmide, N, N'-diisopropylcarbodnmide; l-et? l-3- (3-dimethylaminopropyl) carbodnide (WSCD); N, N '-carbonylbis (2-methylimidazole); pentamethylene ketene-N-cyclohexylimam; diphenyl ketene-N-cyclohexylimam; Etoxyacetylene; 1-alkoxy? -l-chloroethylene; trialquilf osf íto; etilpolif osf ato; isopropyl polyphosphate; phosphorus oxychloride (phosphoryl chloride); phosphorus trichlorhydrate; diphenylphosphorylazide; thionyl chloride; oxalylchloride; lower alkylhaloformate [for example ethylchloroformate, isopropylchloroformate, etc.]; triphenylphosphine; 2-ethyl-7-hydroxybenzisoxazole salt; intramolecular 2-ethyl-5- (m-sulfophenyl) isoxazolium hydroxide salt; N-hydroxybenzotriazole; 1- (p-chlorobenzenesulfonyloxy) -6-chloro-lH-benzotriazole; the reagent called Vilsmeier, prepared by the reaction of N, N-dimethylformamide with thionylchloride, phosgene, trichloromethylchloroformate, phosphorus oxychloride, etc. or similar. The reaction can also be carried out in the presence of an inorganic or organic base, as mentioned above, such as an alkali metal bicarbonate, trialkylamine (lower), pyridine, N-alkylmorpholine. (lower), N, N-dialkylbenzylamine (lower), alkali metal hydroxide, or the like. The reaction temperature is not a critical point and, in general, the reaction is carried out from low to high temperatures. Process 5 The object compound (I-f) or a salt thereof can be prepared by cyclizing the compound (III) or a salt thereof. Suitable salts of the compounds (I-f) and (III) may be the same as those used for the compound (I) • This reaction is preferably carried out in the presence of a hydrogen halide (for example hydrogen iodide, etc.) or an alkali metal halide (for example sodium iodide, etc.). This reaction can be produced in the presence of a convenient base as mentioned above, such as alkali metal hydroxide. The reaction can be carried out in a conventional solvent that does not produce a negative effect on it, such as water, tetrahydrofuran, alcohol (for example methanol, ethanol, etc.), a mixture thereof, and the like. The reaction temperature is not a critical point and, in general, the reaction is carried out from low to high temperatures. Process 6 The compound (Ig) or a salt thereof can be prepared by causing the reaction of the compound (Ib) or its reactive derivative in the carboxy group, or a salt thereof, with an optically active amine or its reactive derivative in the group amino, or a salt thereof. Among the appropriate "optically active amines" is a conventional amine that can separate the original racemic compound in each optically active compound, such as (R) - (+) - methylmethylamine, and similar suitable salts of the compound (Ig) can be the same as indicated for example for the compound (I). Suitable salts of the optically active amine may be the acid addition salts indicated with respect to the compound (I). In general, the reaction is carried out in a conventional solvent such as water, acetone, dioxane, acetonitrile, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, ethyl acetate, N, N-dimethylformamide, pyridine and diclomethane, a mixture of them, or any other organic solvent that does not produce a negative effect on the reaction. This reaction can be carried out in the presence of an organic or inorganic base, such as an alkali metal (for example lithium, sodium, potassium, etc.), an alkaline earth metal (for example calcium, etc.), an alkali metal hydride (for example example, sodium hydride, etc.), an alkaline earth metal hydride (eg, calcium hydride, etc.), an alkali metal hydroxide (eg, sodium hydroxide, potassium hydroxide, etc.), an alkali metal carbonate (for example sodium carbonate, potassium carbonate, etc.) an alkali metal bicarbonate (for example sodium bicarbonate, potassium bicarbonate, etc.), an alkali metal alkoxide (for example sodium methoxide, sodium ethoxide, potassium ter-butoxide, etc.), an alkali metal alkanoic acid (for example sodium acetate, etc.), a trialkylamine (for example triethylamine, etc.), a pyridine compound (for example pyridine, lutidine, picoline, 4-dimethylamino pyridine, etc.) quinoline, lithiodiisopro pilamide, and the like. Among the appropriate reactive derivatives of the optically reactive amine in the amino group is the Schiff base type imino or its tautomeric enamine type isomer formed by the reaction of the indicated amine with a carbonyl compound such as aldehyde, ketone or the like; a silyl derivative formed by the reaction of the indicated amine with a silyl compound such as bis (trimethylsilyl) acetamide, mono (trimethylsilyl) acetamide, bis (trimethylsilyl) urea, or the like; a derivative formed by the reaction of the indicated amine with phosphorus trichloride or phosgene, and the like. The reactive derivatives in the carboxy group and the salts of the appropriate compound (I-b) can be the same as those mentioned above. The reaction is preferably carried out in the presence of a conventional condensing agent such as N, N'-dicyclohexylcarbodiimide; N-cyclohexyl-N '-morpholinylcarbodiimide; N-cyclohexyl-N '- (4-diethylaminocyclohexyl) carbodiimide; N, N '-diethylcarbodiimide; N, N'-diisopropylcarbodiimide; l-ethyl-3- (3-dimethylaminopropyl) carbodiimide; N, N '-carbonylbis- (2-ethylimidazole); pentamethylene ketene-N-cyclohexylimine; diphenylkene-N-cyclohexylimine; Etoxyacetylene; 1-alkoxy-1-chloroethylene; trialkylphosphite; ethyl polyphosphate; isopropyl polyphosphate; phosphorus oxychloride (phosphoryl chloride); phosphorus trichloride; diphenylphosphorylazide; thionyl chloride; oxalylchloride; lower alkylhaloformate (e.g., ethylchloroformate, isopropylchloroformate); triphenylphosphine; 2-ethyl-7-hydroxybenzisoxazole salt; intramolecular 2-ethyl-5- (m-sulfophenyl) isoxazolium hydroxide salt; 1- (p-chlorobenzenesulfonyloxy) -6-chloro-lH-benzotriazole; 1-hydroxybenzotriazole; or the reagent called Vilsmeier prepared from the reaction of N, N-dimethylformamide with thionyl chloride, phosgene, trichloromethylchloroformate, phosphorus oxychloride or oxalyl chloride. The reaction temperature is not a critical point and, in general, the reaction is carried out from low to high temperatures. Process 7 The object compound (I-i) or a salt thereof can be prepared by subjecting the compound (I-h) or a salt thereof to the removal reaction of the protective hydroxyl group. The suitable salts of the compounds (I-h) and (I-i) may be the same as those exemplified for the compound (I). The reaction of this process can be carried out in a manner similar to that indicated for Process 1. Process 8 The compound (I-k) and a salt thereof can be prepared by oxidation of the compound (I-j) or a salt thereof. The suitable salts of the compounds (I-j) and (I-k) may be the same as those mentioned above in relation to the compound (I). Among the appropriate methods of this oxidation are conventional ones, capable of converting this group into a sulfinyl or sulfonyl group, or a sulfinyl group into a sulfonyl group, as exemplified in relation to Process 2. Process 9 The compound (1-1 ) or a salt thereof can be prepared by reacting the compound (Ic) or a salt thereof with the compound (V). Suitable salts of the compound (1-1) may be the same as those indicated in relation to the compound (I).

In general, the reaction occurs in a conventional solvent such as water, acetone, dioxane, acetonitop, chloroform, ethylene chloride, ethylene chloride, tetrahydrofuran, ethyl acetate, N, N-dimethylformamide, pipdma and diclomethane, a mixture of them, or any other organic solvent that does not produce a negative effect on the reaction. This reaction can be carried out in the presence of an organic or inorganic base, such as an alkali metal (for example lithium, sodium, potassium, etc.), an alkaline earth metal (for example calcium, etc.), an alkali metal hydride (for example example, sodium hydride, etc.), an alkaline earth metal hydride (eg, calcium hydride, etc.), an alkali metal hydroxide (eg, sodium hydroxide, potassium hydroxide, etc.), an alkali metal carbonate (for example sodium carbonate, potassium carbonate, etc.) an alkali metal bicarbonate (for example sodium bicarbonate, potassium bicarbonate, etc.), an alkali metal alkoxide (for example sodium methoxide, sodium ethoxide, potassium ter-butoxide, etc.), an alkali metal alkanoic acid (for example sodium acetate, etc.), a trialkylamine (for example triethylamine, etc.), a pyridine compound (for example pipdma, lutidma, picolma, 4-d? Met? Lammo pipdma, etc.) qumolina, lithiodusopropilamide, a hal alkali metal uro (for example sodium iodide, potassium iodide, etc.), an alkali metal thiocyanate (for example sodium thiocyanate, potassium thiocyanate, etc.), a dialkyl (lower) azodicarboxylate (for example diethylazodicarboxylate, dusopropylazodicarboxylate, etc.) and the like. The reaction is preferably carried out in the presence of a conventional condensing agent such as N, N'-dicyclohexylcarbodiimide; N-c? Clohex? L-N '-morphomethylcarbodnmide; N-c? Clohex? L-N '- (4-diethylaminocyclohexyl) carbodiimide; N, N '-diethylcarbodnmide; N, N '-dusopropylcarbodiimide; N-ethyl- N '- (3-d? Met? Lammoprop? L) carbodnmide; N, N '-carbonylbis- (2-met? L? M? Dazol); pentamethylene ketene-N-cyclohexylimam; diphenylkene-N-cyclohexylimine; Etoxyacetylene; 1-alkoxy-1-chloroethene; trialquilf osf íto; etilpolif osf ato; isopropyl polyphosphate; phosphorus oxychloride (phosphoryl chloride); phosphorus tpchloride; diphenylphosphorylazide; thionyl chloride; oxalylchloride; lower alkylhaloformate (e.g., ethylchloroformate, isopropylchloroformate); tpf enilfosf ma; etrakis (triphenylphosphma) palladium (0); salt of 2-et? l-7-hydrox? benc? soxazole? intramolecular 2-et? l-5- (m-sulf of enyl) isoxazolium hydroxide salt; 1- (p-chlorobenzenesulfonyl) -6-chloro-lH-benzotrol; 1-hydroxybenzotriazole; or the reagent called Vilsmeier prepared from the reaction of N, N-dimethylformamide with thionyl chloride, phosgene, trichloromethyl chloroformate, phosphorus oxychloride or oxalyl chloride. The reaction temperature is not a critical point and, in general, the reaction is carried out from low to high temperatures. Process 10 The compound (I-m) or a salt thereof can be prepared by reacting the compound (VI) or a salt thereof with the compound (VII) or a salt thereof. Suitable salts of the compound (I-m) may be the same as those exemplified for the compound (I). The reaction of this process can be carried out in a manner similar to that of Process 9. Process 11 The compound (I-n) or a salt thereof can be prepared by cyclizing the compound (VIII) or a salt thereof. Suitable salts of the compounds (I-n) and (VIII) may be the same as those exemplified for the compound (I). This reaction can be carried out in the presence of an appropriate acid as exemplified for Process 1, where a preferred one may be trifluoroacetic acid, and the like.

The reaction can be carried out in a conventional solvent, which does not influence the reaction in an adverse manner as mentioned above, such as water, tetrahydrofuran, alcohol (for example methanol, ethanol, etc.), a mixture thereof, and the like. The reaction temperature is not critical and the reaction is carried out from low to high temperatures. Process 12 The compound (I-o) or a salt thereof can be prepared by reacting the compound (IX) or a salt thereof with the compound (IX). Suitable salts of the compounds (I-o) and (IX) may be the same as those exemplified for the compound (I). This reaction can be carried out in the presence of an appropriate acid as exemplified for Process 1, where one of the preferred ones can be borohydrochloride triflorurium, and the like. The reaction is usually carried out in a conventional solvent such as water, acetone, dioxane, acetonitrile, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, ethyl acetate, N, N-dimethylformamide, pyridine and dichloromethane, a mixture of the same, or any other organic solvent that does not adversely affect the reaction.

The reaction temperature is not critical and the reaction is carried out from low to high temperatures. Process 13 The compound (I-q) or a salt thereof can be prepared by amidation of the compound (I-p) or its reaction derivative in the carboxy group, or a salt thereof. Suitable salts of the compounds (I-p) and (I-q) may be the same as those for the compound (I). Suitable reaction derivatives of the compound (I-p) may be the same as those for the compound (I-b). The amidation reaction applicable to this process can include a conventional amidation reaction which can convert a carboxy group to an amido group, for example, a reaction with an amine optionally substituted as a mono or dialkylamine (lower) (e.g. methylamine, etc. .), and the like. And the reaction can be carried out basically in the same manner as that described in Process 4. Process 14 The compound (Is) or a salt thereof can be prepared by acylation of the compound (Ir) or its reaction derivative in the group amino, or a salt thereof. Suitable salts of the compounds (I-r) and (I-s) may be the same as those for the compound (I).

The appropriate acylating agent used in this reaction can be a conventional acylating agent which is capable of introducing the acyl group as mentioned above as carboxylic acid, carbonic acid, sulfonic acid and its reaction derivative, for example, acid halide, acid anhydride, activated amide, activated ester, and the like. A preferred example of this reaction derivative may comprise acid chloride, acid bromide, acid anhydride mixed with an acid, such as substituted phosphoric acid (for example dialkylphosphoric acid, phenylphosphoric acid, diphenylphosphoric acid, dibenzylphosphoric acid, halogenated phosphoric acid, etc.), dialkylphosphorous acid, sulphurous acid, thiosulfuric acid, sulfuric acid, alkyl carbonate (for example methylcarbonate, ethylcarbonate, propylcarbonate, etc.), aliphatic carboxylic acid (for example pivalic acid, pentanoic acid, isopentanoic acid, 2-ethylbutyric acid, trichloroacetic acid, etc.), aromatic carboxylic acid (for example benzoic acid, etc.), symmetrical acid anhydride, acid amide activated with a heterocyclic compound, containing the imino function, such as imidazole, substituted 4-imidazole, dimethylpyrazole, triazole and tetrazole, activated ester (for example p-nitrophenylester, 2,4-dinitrophenylester, tr chlorofenilyester, pentachlorophenylester, mesylphenylester, phenylazophenyl ester, phenylthioster, p-nitrophenylthioester, p-cresylthioester, carboxymethyl thioester, pyridylester, piperidinyl ester, 8-quinolyl thioester, or ester with a N-hydroxy compound, such as N, N-dimethylhydroxylamine, 1-hydroxy-2 - (ÍH) -pyridone, N-hydroxysuccinimide, N-hydroxyphthalimide, 1-hydroxybenzotriazole, 1-hydroxy-6-chlorobenzotriazole, etc.), isocyanic acid or a salt thereof (for example sodium isocyanate, etc.), lower alkyl isocyanate (for example methyl isocyanate, ethyl isocyanate, etc.), and the like . This reaction can be carried out in the presence of an organic or inorganic base such as an alkali metal (eg lithium, sodium, potassium, etc.), alkaline earth metal (eg calcium, etc.), alkali metal hydride (eg eg sodium hydride, etc.), alkaline earth metal hydride (eg calcium hydride, etc.), alkali metal hydroxide (eg sodium hydroxide, potassium hydroxide, etc.), alkali metal carbonate (eg for example, sodium carbonate, potassium carbonate, etc.), alkali metal bicarbonate (for example sodium bicarbonate, potassium bicarbonate, etc.), alkali metal alkoxide (for example sodium methoxide, sodium ethoxide, t-butoxide of potassium, etc.), alkanoic acid of alkali metal (for example sodium acetate, etc.), trialkylamine (for example triethylamine, etc.), composed of pipdma (for example pipdin, lutidine, picolma, 4-d? ? lammop? r? d? na, etc.), qumolma, and others. In the case that the acylating agent or its salt is used in the free form in this reaction, it is preferably carried out in the presence of a condensing agent, such as a carbodnide compound [for example N, N '-dicyclohexylcarbodumide, Nc? Clohex? N '- (4-diethylaminocyclohexyl) carbodiimide, N, N' -diethylcarbodumide, N, N '-dusopropylcarbodiimide, N-ethyl- N' - (3-d? Met? Lammoprop? L) carbodnide, etc. ], a ketenimine compound (for example N, N '-carbonylbis (2-methylimidazole), pentamethylene keten-N-cyclohexylimim, diphenylheten-N-cyclohexylimim, etc.); an olefinic or acetylenic ether compound (for example ethoxyacetylene, β-chlorovinylethylether), sulfonic acid ester of an N-hydroxybenzotriazole derivative [for example l- (4-chlorobenzenesulfonyloxy) -6-chloro-lH-benzotrol azol, etc. .], a combination of tpalkylphosphite or triphenylphosphine and carbon tetrachloride, disulfide or diazenedicarboxylate (eg, diethyldiazenedicarboxylate, etc.), a phosphorus compound (eg, ethyl polyphosphate, isopropyl polyphosphate, phosphoryl chloride, phosphorus trichloride, etc.), thionyl chloride, oxalyl chloride, N-ethylbenzoisoxazolium salt, N- et? l-5-phen? l? soxazole? o-3-sulfonate, a reagent (with respect to the so-called "Vilsmeier reagent") formed by the reaction of an amide compound such as N, N-dialkylformamide (lower) or similar (for example, dimethylformamide, etc.), N-methylformamide or the like with a halogenated compound such as thionyl chloride, phosphoyl chloride, phosgene or the like, and others. The reaction is usually carried out in a conventional solvent that does not adversely affect the reaction, such as water, acetone, dichloromethane, alcohol (for example, methanol, ethanol, etc.), tetrahydrofuran, pipdin, N, N-dimethylformamide, etc. , or a mixture thereof. The reaction temperature is not critical and the reaction is carried out from low to high temperatures. Process 15 The compound (I-r) or a salt thereof can be prepared by subjecting the compound (I-t) or a salt thereof to a removal reaction of the protecting group of the one. Suitable salts of the compound (I-t) may be the same as those for the compound (I). The reaction of this process can be carried out in a manner similar to that of Process 1. Process 16 The compound (Iv) or a salt thereof can be prepared by subjecting the compound (Iu) or a salt thereof to a reaction of elimination of the hydroxy protection group. Suitable salts of the compounds (I-u) and (I-v) may be the same as those for the compound (I). The reaction of this process can be carried out in a manner similar to that of Process 1. Process 17 I "The compound (Ix) or a salt thereof can be prepared by oxidation of the compound (Iw) or a salt thereof. Suitable salts of the compounds (I-) and (Ix) can be the same as those for the compound (I). The reaction of this process can be carried out in a manner similar to that of Process 8. Process 18 The The compound (Iz) or a salt thereof can be prepared by reduction of the compound (Iy) or a salt of the same.Suitable salts of the compounds (Iy) and (Iz) can be the same as those for the compound (I) The reaction of this process can be carried out in a manner similar to that of Process 3. Process 19 The compound (I-ab) or a salt thereof can be prepared by oxidation of the compound (I-aa) or a salt thereof Suitable salts of the compounds (I-aa) and (I-ab) may be the same as those for the compound (I). The reaction of this process can be carried out in a manner similar to that of Process 2. Process 20 The compound (I-ac) or a salt thereof can be prepared by acylation of the compound (I-v) or a salt thereof. Suitable salts of the compound (I-ac) may be the same as those for the compound (I). The reaction of this process can be carried out in a manner similar to that of Process 1. Process 21 The compound (I-ad) or a salt thereof can be prepared by reacting the compound (XI) or a salt thereof with the compound (XII) or a salt thereof. Suitable salts of the compounds (I-ad), (XI) and (XII) can be the same as those for the compound (I) • The reaction of this process can be carried out in a manner similar to that of Process 9. Process 22 The compound (Ip) or a salt thereof can be prepared by subjecting the compound (I-ae) or a salt thereof. same to a removal reaction of the carboxy protection group. Suitable salts of the compound (I-ae) may be the same as those for the compound (I). The reaction of this process can be carried out in a manner similar to Process 1. Process 23 The compound (I-ag) or a salt thereof can be prepared by reacting the compound (I-af) or a salt thereof. with a substituted amine. Suitable salts of the compounds (I-af) and (I-ag) may be the same as those for the compound (I). The reaction of this process can be carried out in a manner similar to that of Process 4. The compounds obtained above can be isolated and purified by a conventional method such as spraying, recrystallization, column chromatography, reprecipitation and the like. The compounds of the object can be transformed into their salts in a conventional manner. It should be noted that the subject compounds may include one or more stereoisomers or optical isomers due to the asymmetric carbon atoms, and all such isomers and the mixture thereof are included within the scope of this invention. Collagenases initiate the degradation of collagen in vertebrates and, in addition to their normal function in connective tissue metabolism and wound healing, they have been implicated in numerous pathological conditions such as joint destruction in rheumatoid arthritis, disease periodontal disease, corneal ulceration, tumor metastasis, osteoarthritis, decubitus restenosis after percutaneous transluminal coronary angioplasty, osteoporosis, psoriasis, chronic active hepatitis, autoimmune keratitis and the like, and consequently, The present invention is useful for treating and / or preventing such pathological conditions. The inhibitory activity of MMP can be tested by the conventional test method mentioned below. Test Methods: Test Method 1: Inhibitory activity of human MMP-1 Human collagenase was prepared from the human skin fibroblast culture medium stimulated with interleukin-lβ (1 mg / ml). The latent collagenase was activated by incubation with trypsin (200 μg / ml) at 37 ° C for 60 minutes and the reaction was stopped by adding soybean trypsin inhibitor (800 μg / ml). Collagenase activity was determined using type I collagen from calf skin labeled with FITC. Collagen with FITC (2.5 mg / ml) was incubated at 37 ° C for 120 minutes with the activated collagenase and the compound under test in 50 mM Tris buffer (containing 5 mM CaCl2, 200 mM NaCl and 0.02% of NaN3, pH 7.5). After stopping the enzyme reaction by adding an equal volume of 20% ethanol and 200 mM Tris buffer (pH 9.5), the reaction mixture was centrifuged and the activity of the collagenase was estimated by measuring the fluorescence intensity of the supernatant at 495 nm (excitation) and at 520 nm (emission). Test Method 2: Inhibitory activity of human MMP-9 The inhibitory activity of the compounds under test against human MMP-9 was measured using commercial packs (Yagai, Japan). The gelatinolytic activity was determined by monitoring the degradation of bovine type IV collagen labeled with FITC after incubation for 4 hours at 42 ° C. The amount of collagen degraded was estimated by measuring the intensity of the fluorescence at 495 nm (excitation) and at 520 nm (emission). Test Method 3: Inhibitory Activity of Human MMP-13 The inhibitory potential of the compounds tested against human MMP-13 was tested using the commercial kit (Chondrex, USA) containing the truncated form of human recombinant MMP-13. and fluorogenic peptide substrate. The inhibitory activity of human MMP-13 was determined by monitoring the degradation of the fluorogenic peptide substrate after incubation for 1 hour at 35 ° C and was estimated by measuring the intensity of the fluorescence of the degraded peptide substrate at 495 nm (excitation) and at 520 nm (emission). Test Method 4: Inhibitory activity of human MMP-8 The inhibitory potential of the compounds tested against human MMP-8 was tested using the commercial kit (Chondrex, USA) containing recombinant human pro-MMP-8 and collagen from Type I bovine soluble telopeptide-free labeled with FITC as a substrate. Recombinant human pro-MMP-8 was activated by sequential incubation with a mercury compound and proteinase at 35 ° C for 1 hour. The reaction mixture containing activated MMP-8, the substrate and the compounds under test was incubated at 35 ° C for 2 hours. After stopping the reaction of the enzyme by adding the stopping solution (o-phenatroline), the reaction mixture was centrifuged and the activity of MMP-8 was estimated by measuring the intensity of the fluorescence of the supernatant at 490 nm (excitation) and at 520 nm (emission). For therapeutic purposes, the compounds and pharmaceutically acceptable salts thereof of the present invention were used in the form of a pharmaceutical preparation containing, as an active ingredient, one of the compounds mixed with a pharmaceutically acceptable carrier such as a solid or liquid excipient. organic or inorganic suitable for oral, parenteral or external administration. The pharmaceutical preparations can be capsules, tablets, dragees, granules, solutions, suspensions, emulsions, sublingual tablets, suppositories, ointments and the like. If desired, auxiliary substances, stabilizing agents, wetting agents, emulsifying agents, buffers and other commonly used additives may be included in these preparations. Although the dose of the compound varies according to the age and condition of the patient and similar aspects, in the case of intravenous administration, a daily dose of 0.01 to 100 mg of the active ingredient per kg of weight of a human being is generally given. , and in the case of intramuscular administration, a daily dose of 0.05 to 100 mg thereof per kg of weight of a human being, or in the case of oral administration, a daily dose of 0.1 to 100 mg thereof per kg. of a human being, for the treatment of MMP or diseases mediated by TNFa. To illustrate the utility of the compound object of the invention, the data of the pharmacological tests of a compound representative of the compounds are shown below: MMP Inhibitory Activity 1. Test Method Inhibitory activity of the human MMP-13 mentioned above. 2. Compound Assay Compound of Example 15 3. Test Result The following preparations and examples are given for the purpose of illustrating the present invention in detail. The abbreviations used in this description are, for example, the following: Aib: aminoisobutyric acid Abu: inobutyric acid 4PiAla: 4-pyridylalanine Preparation 1-1) N-chlorosuccinimide (2.67 g) was gradually added for more than 30 minutes to a stirring solution of tetrahydro-2H-thiopyran (2.04 g) in benzene (20 ml). The temperature was maintained between 20-30 ° C with an intermittent external cooling. The mixture was stirred for 1 hour and filtered rapidly to remove the succinimide. The filtrate was added to a solution of 4-anisylmagnesium bromide in diethylether which was prepared from 4-anisyl bromide (7.48 g) and variations of magnesium (0.875 g) in diethyl ether (36 ml) in a usual manner. The rate of aggregation was such that the reaction temperature was maintained between 10-15 ° C. The resulting mixture was stirred at room temperature for 17 hours and decomposed by the addition of ice and an aqueous solution of 20% sulfuric acid. The organic layer was separated, washed twice with water, once with a solution of sodium hydroxide, twice with water, then once with brine, and dried over magnesium sulfate. The solvent was removed, followed by washing with methanol, and gave 3, 4, 5, 6-tetrahydro-2- (4-methoxyphenyl) -2H-thiopyran (1.22 g) as a colorless powder. melting point: 82-85 ° C IR (KBr): 1610, 1514, 1252 cm "1 NMR (DMSO-dg, d): 1.35-1.65 (2H, m), 1.7-2.1 (4H, m), 2.56 -2.64 (ÍH, m), 2.73-2.86 (ÍH, m), 3.72 (3H, s), 3.84 (ÍH, dd, J = 11.0, 2.7Hz), 6.87 (2H, d, J = 8.7Hz), 7.24 (2H, d, J = 8.7Hz) Anal heat, for C] 2HX6OS: C 69.19, H 7.74 Found: C 69.59, H 7.68 Preparation 1-2) An l.OM solution of boron tribromide in dichloromethane (8.27 ml) was added dropwise to a stirred solution of 3,5,6-tetrahydro-2- (4-methoxyphenyl) -2H-thiopyran (718 mg) in dichloromethane (10 ml) under ice-cooling, and the resulting mixture it was stirred for 3 hours while the temperature was raised to room temperature.The reaction mixture was evaporated in vacuo and the residue was partitioned between ethyl acetate and water.The organic layer was separated, washed with brine, dried over sodium sulfate, The residue was chromatographed (eluant: toluene-ethyl acetate) on silica gel (15.4 g) to remove the residue and evaporated in vacuo. obtain 3,4,5,6-tetrahydro-2- (4-hydroxyphenyl) -2H-thiopyran (600 mg) as a colorless powder. Melting point: 138-140.5'C IR (KBr): 3421 (br), 1241 cm "1 NMR (DMSO-d6, d): 1.35-1.65 (2H, m), 1.7-2.05 (4H, m), 2.58 (HH, br d, J = 13.3 Hz), 2.71- 2.85 (HH, m), 3.78 (HH, dd, J = 10.8, 2.5Hz), 6.68 (2H, d, J = 8.5Hz), 7.11 ( 2H, d, J = 8.5Hz), 9.32 (HH, s) Preparation 1-3) A mixture of 3, 4, 5, 6-tetrahydro-2- (4-hydroxyphenyl) -2H-thiopyran (578 mg), 4-Bromochlorobenzene (683 mg), 8-hydroxyquinoline (17.3 mg), potassium carbonate (247 mg), and copper (I) chloride (11.8 mg) in 1,3-dimethyl-2-imidazolidinone (1.73 g) were stirred at 150 ° C under a nitrogen atmosphere for 21 hours and cooled to room temperature The reaction mixture was partitioned between ethyl acetate and water.The organic layer was separated, washed with an aqueous solution of sodium hydroxide and brine, dried over magnesium sulfate, and evaporated in vacuo The residue was chromatographed (eluent: n-hexane-toluene) on silica gel to obtain 2- [4- (4-chlorophenoxy) phenyl] -3,4 , 5, 6-tetrahydro-2H-thiopyran (417 mg) as a colorless powder. Melting point: 69.5-70.5 ° C IR (KBr): 1274 cm "1 NMR (CDC13, d): 1.45-1.77 (2H,), 1.83-2.2 (4H, m), 2.66 (1H, m), 2.81 -2.95 (HH, m), 3.84 (HH, dd, J = 11.6, 2.6Hz), 6.88-6.97 (4H, m), 7.23-7.36 (4H, m) Preparation 1-4) An aqueous solution (23 ml) ) of OXONE (2KHS05.KHS04.K2S04, 1.82g) was added dropwise to a suspension of 2- [4- (4-chlorophenoxy) phenyl] -3,5,6-tetrahydro-2H-thiopyran (600 mg) in methanol ( 23 ml) under cooling with ice, and the resulting mixture was stirred at room temperature for 17 hours. The reaction mixture was mixed with an aqueous solution (10 ml) of sodium sulfite (746 mg) at room temperature, stirred at the same temperature for a while, and concentrated in vacuo. The residue was partitioned between ethyl acetate and water, the organic layer was separated, washed with brine, dried over sodium sulfate, and evaporated in vacuo. The residue was washed with n-hexane to obtain 2- [4- (-chlorophenoxy) -phenyl) -3,4,5,6-tetrahydro-2H-thiopyran-1,1-dioxide (636 mg) as a colorless powder . Melting point: 151.5-152"C IR (KBr): 1313, 1247, 1120 cm" 1 NMR (CDC13, d): 1.65 (H, m), 2.04-2.26 (4H, m), 2.37-2.56 (H) ,), 2.96-3.13 (ÍH, m), 3.24 (ÍH, m) 4.01 (ÍH, dd, J = 12.8, 3.1Hz), 6.92- 7.03 (4H, m), 7.28-7.42 (4H, m) ( +) APCl MS m / z: 336 (M + + H) Preparation 1-5) A 1.5M solution of monotetrahydrofuran of lithium diisopropylamide in cyclohexane (1.47 ml) was added dropwise to a stirred suspension of 1,1-dioxide from 2- [4- (4-chlorophenoxy) phenyl] -3,, 5,6-tetrahydro-2H-thiopyran (621 mg) in tetrahydrofuran (9 ml) under a nitrogen atmosphere and cooling with dry ice-acetone and suspension The resulting mixture was stirred under the same conditions for 25 minutes. A solution of allyl bromide (491 mg) in tetrahydrofuran (2.5 ml) was added dropwise and the resulting mixture was stirred under the same conditions for 2 hours and 30 minutes. After adding a saturated aqueous solution of ammonium chloride under the same conditions, the reaction mixture was extracted with ethyl acetate. The extract was washed successively with IN hydrochloric acid, brine and a saturated aqueous solution of sodium bicarbonate, dried over magnesium sulfate, and evaporated in vacuo. The residue was chromatographed (eluent: toluene-ethyl acetate) on silica gel to obtain 2-allyl-2- (4- (4-chlorophenoxy) phenyl] -3, 4, 5, 6-1,1-dioxide. tetrahydro-2H-thiopyran (419 mg) as a colorless oil IR (film): 1639, 1311, 1243, 1126 cm "1 NMR (CDC13, d): 1.81-1.86 (2H, m), 2.09-2.21 (3H , m), 2.53-2.68 (HH, m), 2.86-3.09 (2H, m), 3.17-3.35 (2H, m), 5.02-5.09 (HH, m), 5.14-5.31 (2H, m), 6.94 -7.05 (4H, m), 7.31 (2H, d, J = 9.0Hz), 7.61 (2H, d, J = 9.0Hz) (+) API-ES MS m / z: 399 and 401 (M ++ Na ) Preparation 1-6) A 1.5M solution of monotetrahydrofuran diisopropylamide lithium in cyclohexane (0.34 ml) was added dropwise to a stirred solution of 2-allyl-2- [4- (4-chlorophenoxy) 1,1-dioxide) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran (162 mg) in tetrahydrofuran (2.5 ml) under a nitrogen atmosphere and cooling with dry ice-acetone and the resulting solution was stirred under the same conditions for 30 minutes. minutes, a solution of yodu The methyl ester (134 mg) in tetrahydrofuran (0.5 ml) was added dropwise and the resulting mixture was stirred under the same condition for 1 hour and 20 minutes. After adding a saturated aqueous solution of ammonium chloride under the same conditions, the reaction mixture was extracted with ethyl acetate. The extract was washed successively with hydrochloric acid and brine, dried over sodium sulfate, and evaporated in vacuo. The residue was chromatographed (eluent: toluene-ethyl acetate) on silica gel (8.1 g) to obtain 2-allyl-2- [4- (4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-6-methyl-2H-thiopyran 1,1-dioxide (78 mg) like a pasta. IR (KBr): 1639, 1284, 1244, 1126 crn "1 NMR (CDC13, d): 1.38 (3H, d, J = 6.7Hz), 1.82-2.25 (5H, m), 2.61 (ÍH, m), 2.99 (ÍH, dd, = 14.3, 7.7Hz), 3.32-3.39 (2H, m), 5.02-5.08 (ÍH, m), 5.16-5.29 (2H, m), 6.95-7.03 (4H, m), 7.28 -7.33 (2H, m), 7.57-7.64 (2H, m) (+) APCl MS m / z: 391 and 393 (M ++ H) Preparation 2 2- [4- (4-chlorophenoxy) phenyl] -3 ,, 5,6-tetrahydro-2H-thiopyran (148 mg) was prepared from 3,4,5,6-tetrahydro-2- (4-hydroxyphenyl) -2H-thiopyran (292 mg) and 4-chloroiodobenzene ( 430 mg) in a manner similar to that of preparation 1-3) Melting point: 69.5-70.5 ° C Preparation 3 2- [4- (4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro -2H-thiopyran (97 mg) was prepared from tetrahydro-2H-thiopyran (510 mg) and 4-bromo-4'-chlorodiphenyl-ether (2.12 g) in a manner similar to that of preparation 1-1) Melting point: 69.5-70.5 ° C Preparation 4-1) 5-Chlorovaleryl chloride (17.1 g) was added dropwise to a stirred suspension of aluminum chloride (14.7 g) ) in dichloromethane (125 ml) under a nitrogen atmosphere and ice-cooling for more than 5 minutes, and the resulting solution was stirred under the same conditions for 10 minutes, then a 4-chlorodiphenyl ether solution was added dropwise ( 20.5 g) in dichloromethane (115 ml) for more than 20 minutes. The resulting mixture was stirred under the same conditions for 1 hour and 15 minutes, and poured into a mixture of 7% hydrochloric acid and ice. The organic layer was separated, washed with brine, dried over sodium sulfate, and evaporated in vacuo. The oily residue was pulverized from n-hexane to obtain 4- (5-chlorovaleryl) -4'-chlorodiphenyl-ether (30.9 g) as a colorless powder. Melting point: 59.5-60.5 ° C IR (KBr): 1672, 1250 crn "1 NMR (CDC13, d): 1.85-1.91 (4H, m), 2.94-3.02 (2H, m), 3.55-3.62 (2H ,), 6.96-7.05 (4H, m), 7.36 (2H, d, J = 9.0Hz), 7.95 (2H, d, J = 8.9Hz) (+) API-ES MS m / z: 345, 347 y 349 (M + + Na) Preparation 4-2) A solution of sodium borohydride (2.16 g) in water (59 ml) was added dropwise to a stirred suspension of 4- (5-chlorovaleryl) -4'-chlorodiphenyl ether (30.8 g) and sodium bicarbonate (9.61 g) in ethanol (480 ml) under an atmosphere of nitrogen. at room temperature for more than 10 minutes, and the resulting mixture was stirred under the same conditions for 3 hours. After removing the ethanol, the reaction mixture was acidified with 3N hydrochloric acid (70 ml) and extracted with toluene. The extract was washed successively with water, a saturated aqueous solution of sodium bicarbonate and brine, dried over sodium sulfate, and evaporated in vacuo to obtain 4- (5-chloro-1-hydroxypentyl) -4'-chlorodiphenyl- ether (31.1 g) as a yellow oil. IR (film): 3383 (br), 1242 c "1 NMR (CDC13, d): 1.43-1.89 (7H, m), 3.53 (2H, t, J = 6.6Hz), 4.67 (ÍH, m), 6.89 -7.01 (4H, m), 7.24-7.34 (4H, m) (+) API-ES MS m / z: 347, 349 and 351 (M + + Na), 311 and 313 (M + -HCl + Na) Preparation 4-3) Thionyl chloride (31.2 g) was added dropwise to a stirred solution of 4- (5-chloro-l-hydroxypentyl) -4'-chlorodiphenyl ether (31.0 g) in chloroform (383 ml) under cooling with ice, and the resulting solution was stirred under reflux for 4 hours.The reaction mixture was cooled to room temperature and evaporated in vacuo.The residue was partitioned between toluene and water, the organic layer was separated, washed with a solution saturated aqueous sodium bicarbonate (twice) and brine, dried over sodium sulfate, and evaporated in vacuo, to obtain 4-chloro-4 '- (1,5-dichloropentyl) diphenyl ether (33.7 g) as a pale brown oil IR (film): 1242 cm "1 NMR (CDC13, d): 1.47-1.85 (4H, m), 2.02-2.19 (2H, m), 3.53 (2H, t, J = 6.5Hz), 4.85 (HH, dd, J = 7.9, 6.6Hz), 6.91-7.00 (4H, m), 7.27- 7.38 (4H,) Preparation 4-4) Sulfur nonahydrate Sodium (21.8 g) was added gradually to a stirred solution of 4-chloro-4 '- (1,5-dichloropentyl) diphenyl ether (24.0 g) in N, N-dimethylformamide (DMF, 240 ml) under ice-cooling and a nitrogen atmosphere, and the resulting mixture was stirred under the same conditions for 2 hours and at room temperature for 3 days, then the reaction mixture was filtered. The filtrate was concentrated in vacuo and partitioned between water and toluene. The organic layer was separated, washed twice with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was chromatographed (eluent: n-hexane-toluene) on silica gel to obtain 2- [4- (4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran (13.8 g) as a colorless powder. Melting point: 69.5-70.5 ° C Preparation 5-1) 5- (4-chlorophenyl) -2- (5-chlorovaleryl) thiophene (3.75 g) was obtained in a manner similar to that of preparation 4-1). NMR (CDC13, d): 1.86-1.95 (4H, m), 2.95 (2H, dd, J = 6.9, 6.9Hz), 3.59 (2H, dd, J = 6.9, 6.9Hz), 7.30 (ÍH, d, J = 3.9 Hz), 7.39 (2H, d, J = 8.4Hz), 7.58 (2H, d, J = 8.4Hz), 7.67 (IH, d, J = 3.9Hz) Preparation 5-2) 7-chloro- Ethyl 3- [5- (4-chlorophenyl) -2-t? In? L] hept-2-enoate (4.2 g) was obtained in a manner similar to that of Preparation 8-2). NMR (CDCl ,, d): 1.21-1.34 (3H, m), 1.61-1.93 (4H, m) 2.53-2.57 (HH, m), 3.06-3.11 (HH, m), 3.52-3.60 (2H, m) ), 4.12-4.23 (2H, m), 5.88 (0.5H, s), 6.23 (0.5H, s), 7.21-7.34 (4H, m), 7.51-7.53 (2H,) Preparation 6-1) Third Potassium butoxide (1.34 g) was added gradually to a stirred solution of 4-chloro-4 '- (1,5-dichloropentyl) diphenylether (3.44 g) and thiobenzoic acid (1.66 g) in N, N-dimethylformamide (48 ml) under cooling with ice and a nitrogen atmosphere for 5 minutes, and the resulting mixture was stirred at the same temperature for 2 hours and at room temperature for 16 hours.

The reaction mixture was partitioned between ethyl acetate and an aqueous solution of sodium bicarbonate. The organic layer was separated, washed with a saturated aqueous sodium bicarbonate solution and brine, dried over magnesium sulfate, and evaporated in vacuo. The oily residue (4.63 g) was chromatographed (eluent: n-hexane-toluene) on silica gel to obtain 4- (1-benzoyl-5-chloropentyl) -4'-chlorodiphenylether (1.16 g) like a pink oil. IR (film): 1660, 1242 c "1 NMR (CDC13, d): 1.36-1.65 (2H, m), 1.75-1.90 (2H, m), 1.99-2.12 (2H, m), 3.52 (2H, t, J = 6.6Hz) , 5 4.77 (1H, t, J = 7.8Hz), 6.90-6.98 (4H, m), 7.25-7.57 (7H, m), 7.90-7.96 (2H, m) (+) API-ES MS m / z : 467, 469 and 471 (M + + Na) Preparation 6-2) ^^ A solution of 28% sodium methoxide in methanol (J (96.5 mg) was added dropwise to a stirred solution of 4- (l- benzoylthio-5-chloropentyl) -4'-chlorodiphenylether (223 mg) in methanol (1.1 ml) and acetonitrile (1.1 ml) under cooling with ice, and the resulting mixture was stirred at the same temperature for 2 hours, then 5 hours were added thereto. An additional 28% sodium methoxide solution in methanol (96.5 mg), methanol (1.0 ml) and sodium iodide (7.5 mg) was added and the mixture was stirred at room temperature for 15 hours.The reaction mixture was acidified with acid 3N hydrochloric acid (0.5 ml) under cooling with ice The acidified mixture was extracted with toluene, the extract was washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue (197 mg) was chromatographed (eluent: n-hexane-toluene) on silica gel (3.9 g) to obtain 2- [4- (4-chlorophenoxy) phenyl] -5,3,4,5,6-tetrahydro -2H-thiopyran (114 mg) as a colorless powder. Melting point: 69.5-70.5'C Preparation 7-1) 4- (4-chlorobutyryl) -4'-chlorodiphenylether (6.12 g) was prepared from 4-chlorobutyryl chloride (3.10 g) and 4-chlorodiphenylether (4.09 g) in a manner similar to that of preparation 4-1). IR (film): 1680, 1250 cm "1 ^ NMR (CDC13, d): 2.22 (2H, m), 3.14 (2H, t, J = 7.0Hz), lú 3.68 (2H, t, J = 6.2Hz) , 6.96-7.05 (4H, m), 7.31- 7.40 (2H, m), 7.93-8.01 (2H, m) Preparation 7-2) 4- (4-chloro-l-hydroxybutyl) -4'-chlorodiphenylether (6.14) g) was prepared in a manner similar to that of preparation 5 4-2). NMR (CDC13, d): 1.76-2.01 (4H, m), 3.51-3.64 (2H, m), 4.70 (1H, m) , 6.90-7.00 (4H, m), 7.24-7.34 (4H, m) (+) API-ES MS m / z: 333, 335 and 337 (M + + Na) 0 Preparation 7-3) 4-chloro- 4 '- (1,4-dichlorobutyl) diphenyl ether (5.75 g) was prepared in a manner similar to that of preparation 4-3). IR (film): 1244 cm "1 NMR (CDCl 3, d): 1.72-2.30 (4H, m), 3.57 (2H, t, 5 J = 6.4Hz), 4.88 (H, t, J = 7.2Hz), 6.89-7.00 (4H, m), 7.24-7.39 (4H, m) (+ ) API-ES MS m / z: 293 and 295 (M + -C1) Preparation 7-4) 2- [4- (4-chlorophenoxy) phenyl] -2, 3, 4, 5-tetrahydrothiophene (3.63 g) was prepared in a similar way to that of preparation 4-4). IR (film): 1238 cm "1 NMR (CDC13, d): 1.87-2.02 (2H, m), 2.23-2.44 (2H, m), 2.99-3.17 (2H, m), 4.50 (ÍH, dd, J = 8.4, 6.0Hz), 6.88-6.97 (4H, m), 7.23-7.31 (2H, m), 7.36 (2H, d, J = 8.5Hz) Preparation 7-5) 2- [1,1-dioxide] 4- (4-chlorophenoxy) phenyl) -2, 3, 4, 5-tetrahydrothiophene (3.05 g) was prepared in a manner similar to that of preparation 1-4.) Melting point: 74.5-78.5 ° C IR ( film): 1315, 1234, 1169, 1126 cm "1 NMR (CDC13, d): 2.18-2.55 (4H, m), 3.12-3.36 (2H, m), 4.14 (ÍH, dd, J = 11.7, 7.3Hz ), 6.92- 7.05 (4H, m), 7.28-7.39 (4H, m) (+) APCl MS m / z: 323 and 325 (M ++ H) Preparation 8-1) To a suspension of aluminum chloride ( 3.58 g) in methylene chloride (20 ml) was added a solution of 5-chlorovaleryl chloride (4.17 g) in methylene chloride (5 ml) by dripping at 0 ° C. After being stirred for 30 minutes at the same temperature, a solution of 4-chlorodiphenylether (6 g) in methylene chloride (5 ml) was added and the mixture was stirred under cooling with ice bath for 2 hours. Then 4N hydrochloric acid was carefully added to decompose the excess aluminum chloride, the organic layer was separated and the aqueous layer was extracted with chloroform (20 ml x 2). The combined organic layer was washed with water and brine, and concentrated under reduced pressure. The resulting residue was washed with hexane to form 4- (5-chlorovaleryl) -4'-chlorodiphenylether (6.89 g) as a light yellow solid. NMR (DMSO-d6, d): 1.84-1.95 (4H, m), 2.99 (2H, t, J = 7Hz), 3.42 (2H, t, J = 7Hz), 6.99 (2H, d, J = 9Hz) , 7.00 (2H, d, J = 9Hz), 7.37 (2H, d, J = 9Hz), 7.96 (2H, d, J = 9Hz) Preparation 8-2) To a suspension of sodium hydride (dispersion in oil to 60%, 3.14 g) in tetrahydrofuran (160 ml) was added a solution of triethyl phosphonoacetate (5.23 ml) in tetrahydrofuran (20 ml) at 0 ° C. After stirring for 30 minutes at the same temperature, a solution of 4- (5-chlorovaleryl) -4'-chlorodiphenylether (48 g) in tetrahydrofuran (60 ml) was added, and the reaction mixture was refluxed during refluxing. night. The mixture was cooled to room temperature, poured into water, and concentrated under reduced pressure. The residue was extracted with ethyl acetate (200 ml x 3). The combined extract was washed with brine, dried over magnesium sulfate and concentrated to form ethyl 7-chloro-3- [4- (4-chlorophenoxy) phenyl] hept-2-enoate (E: Z-1: 1 mixture) (67.4 g) as a yellow oil. NMR (CDC13, d): 1.14 (1.5H, t, J = 7Hz), 1.26 (1.5H, t, J = 7Hz), 1.29-1.40 (2H, m), 1.50- 1.67 (2H, m), 1.74 -1.89 (2H, m), 2.45 (1.5H, t, J = 7Hz), 3.09 (1.5H, t, J = 7Hz), 3.51 (IH, t, J = 7Hz), 3.53 (IH, t, J = 7Hz), 4.03 (HH, q, J = 7Hz), 4.14 (HH, q, J = 7Hz), 5.89 (0.5H, s), 6.04 (0.5H, s), 6.90-7.01 (4H, m) , 7.14 (2H, d, J = 8Hz), 7.28 (IH, d, J = 8Hz), 7.30 (IH, d, J = 8Hz), 7.42 (2H, d, J = 8Hz) Preparation 8-3) One Solution of sodium iodide (128 g) and ethyl 7-chloro-3- [4- (4-chlorophenoxy) phenyl] hept-2-enoate (67.4 g) in acetone (200 ml) was refluxed for 24 hours . The resulting mixture was poured into water (300 ml) and extracted with ethyl acetate (100 ml x 2). The combined organic layer was washed with water and brine, and dried over magnesium sulfate to form ethyl 3- [4- (4-chlorophenoxy) phenyl] -7-iodo-hepty-2-enoate (67.8 g) (E : Z1: 1 mix) as a yellow oil.

NMR (CDC13, d): 1.14 (1.5H, t, J = 7Hz), 1.26 (1.5H, t, J = 7Hz), 1.29-1.37 (2H, m), 1.46- 1.62 (2H, m), 1.78 -1.94 (2H, m), 22.44 (1.5H, t, J = 7Hz), 3.12 (1.5H, t, J = 7Hz), 5 3.18 (3H, t, J = 7Hz), 4.04 (ÍH, q, J = 7Hz), 4.20 (ÍH, q, J = 7Hz), 5.88 (0.5H, s), 6.04 (0.5H, s), 6.89-7.00 (4H, m), 7.14 (2H, d, J = 8Hz ), 7.26-7.36 (3H, m), 7.42 (2H, d, J = 8Hz) ltr Preparation 8-4) A mixture of 3- [4- (4-chlorophenoxy) phenyl] -7-iodo-hept-2 ethyl acetate (59.8 g) and thiourea (9.39 g) in ethanol (123 ml) was refluxed for 24 hours. The resulting mixture was cooled and evaporated to form 7-amidinothio-3- [4- (4-chlorophenoxy) phenyl] hept-2-enoate ethyl ester (70.2 g) iodide (E: Z = 1: 1 mixture) as a slightly yellow oil. NMR (DMSO-d6, d): 1.05 (1.5H, t, J = 7Hz), 1.24 (1.5H, t, J = 7Hz), 1.33-1.68 (4H, m), 2.48 0 (ÍH, t, J = 7Hz), 3.05-3.16 (3H, m), 3.96 (HH, q, J = 7Hz), 4.12 (HH, q, J = 7Hz), 5.93 (0.5H, s), 6.07 (0.5H, s) , 6.96-7.13 (4H, m), 7.20 (HH, d, J = 8Hz), 7.46 (HH, d, J = 9Hz), 7.48 (HH, d, J = 8Hz), 7.60 (HH, d, J = 8Hz) 5 MS (ES-) m / z: 433 (MH) Preparation 9-1) 4- (5-chlorovaleryl) -4 '-fluorodiphenylether (3.86 g) was obtained in a manner similar to that of Preparation 4 -1) . NMR (CDC13, d): 1.81-1.92 (4H, m), 2.97 (2H, dd, J = 7.7Hz), 3.53-3.6 (2H, m), 6.94-7.12 (6H, m), 7.92-7.95 (2H, m) Preparation 9-2) 7-Chloro-3- [4- (4-fluorophenoxy) phenyl] hept-2-enoate (1.90 g) was obtained in a manner similar to that of preparation 8- 2). NMR (CDCI3, d): 1.31 (3H, dd, J = 7, 7Hz), 1.54- 1.64 (2H, m), 1.78-1.88 (2H, m), 3.12 (2H, dd, J = 7.5, 7.5Hz ), 3.53 (2H, dd, 3 = 1, 7Hz), 4.20 (2H, ddd, J = 7, 7, 7Hz), 6.03 (ÍH, s), 6.93-7.09 (6H, m), 7.39-7.42 ( 2H, m) Preparation 10-1) 4- (5-chlorovaleryl) -4'-bromodiphenylether was obtained (6.71 g) in a manner similar to that of preparation 4-1).

NMR (CDCI3, d): 1.82-1.94 (4H, m), 2.99 (2H, t, J = 6.5Hz), 3.60 (2H, t, J = 6.5Hz), 6.95 (2H, d, J = 9Hz) , 7.00 (2H, d, J = 9Hz), 7.51 (2H, d, J = 9Hz), 7.95 (2H, d, J = 9Hz) Preparation 10-2 3- [4- (4-bromophenoxy) phenyl was obtained ] -7-chlorohept-2-ethyl acetate (7.55 g) in a manner similar to that of preparation 8-2). NMR (CDC13, d): 1.14 (1.5H, t, J = 7Hz), 1.21-1.39 (1.5H, m), 1.49-1.65 (2H, m), 1.74-1.88 (2H, 5 m), 2.47 ( ÍH, t, J = 7Hz), 3.12 (ÍH, t, J = 7Hz), 3.47-3.56 (2H,), 4.03 (ÍH, q, J = 7Hz), 4.20 (ÍH, q, J = 7Hz), 5.89 (0.5H, s), 6.04 (0.5H, s), 6.86-6.99 (4H, m), 7.39-7.50 A (4H, m) (J Preparation 10-3) 3- [4- (4 -bromophenoxy) phenyl] -7-iodohept-2-enoate ethyl ester (7.85 g) in a manner similar to that of preparation 8-3). NMR (CDC13, d): 1.14 (1.5H, t, J = 7Hz), 1.21-1.39 5 (1.5H, m), 1.49-1.65 (2H, m), 1.74-1.88 (2H, m), 2.47 ( ÍH, t, J = 7Hz), 3.12 (ÍH, t, J = 7Hz), 3.47-3.56 (2H,), 4.03 (ÍH, q, J = 7Hz), 4.20 (ÍH, q, J = 7Hz), 5.89 (0.5H, s), 6.04 (0.5H, s), 6.66-6.99 (4H, m), 7.39-7.50 0 (4H, m) Preparation 10-4) 7-Amidinothio-3- [-] iodhydrate was obtained Ethyl (4- bromophenoxy) phenyl] hept-2-enoate (10.4 g) in a manner similar to that of preparation 9-4). 5 NMR (DMSO-d6, d): 1.06 (1.5H, t, J = 7Hz), 1.24 (1.5H, t, J = 7Hz), 1.35-1.52 (2H, m), 1.54- 1.75 (2H,) , 3.06-3.17 (2H, m), 3.39-3.49 (2H, m), 3.94 (HH, q, J = 7Hz), 4.15 (HH, q, J = 7Hz), 5.94 (0.5H, s) , 6.07 (0.5H, s), 6.96-7.11 (4H, m), 7.56-7.64 (4H, m), 9.01- 9.15 (4H,) MS (ESI +) m / z: 479, 563 (+ TFA) Preparation 11-1) Methyl-4- (5-chlorovaleryl) phenyl ether (8.77 g) was obtained in a manner similar to that of preparation 4-1). NMR (CDC13, d): 1.84-1.94 (4H, m), 2.97 (2H, t, J = 7Hz), 3.59 (2H, t, J = 6.5Hz), 3.88 (3H, s), 6.94 (2H, d, J = 9Hz), 7.95 (2H, d, J = 9Hz) Preparation 11-2) To a stirred solution of lithium diisopropylamide in tetrahydrofuran (prepared from diisopropylamine (2.32 g) and n-lithiobutyl (14.3 ml, 1.6 M in n-hexane) in tetrahydrofuran (14 ml) was added dropwise Ethyl acetate (2.80 g) was maintained at -60 ° C in a bath with dry acetone ice.The mixture was stirred for 1 hour at -60 ° C and quenched with the addition of saturated aqueous ammonium chloride. ethyl acetate The organic phase obtained was washed three times with saturated aqueous ammonium chloride and brine, dried over sodium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel (eluted with 5-10% ethyl acetate in n-hexane) to form ethyl 7-chloro-3-hydroxy-3- (4-methoxyphenyl) -heptanoate ( 3.56 g) as an oil. NMR (CDC13, d): 1.12 (3H, t, J = 7.5Hz), 1.16-1.30 (HH, m), 1.39-1.56 (HH,), 1.62-1.82 (4H, m), 2.77 (HH, d , J = 16 Hz), 2.94 (ÍH, d, J = 16Hz), 3.45 (2H, t, J = 6.5Hz), 3.80 (3H, s), 4.04 (2H, q, J = 7.5Hz), 4.38 (ÍH, s), "6.86 (2H, d, J = 9Hz), 7.31 (2H, d, J = 9Hz) Preparation 11-3) A mixture of 7-chloro-3-hydroxy-3- (4-methoxyphenyl) ethyl heptanoate (3.55 g), potassium thioacetate (1.42 g) and a catalytic amount of tetrabutyl ammonium iodide (n-Bu4NI) (150 mg) in N, N-dimethylformamide (30 ml) was stirred for 6 hours at The mixture was poured into saturated aqueous ammonium chloride and extracted with ethyl acetate.The organic phase was washed three times with saturated aqueous ammonium chloride and brine, dried over sodium sulfate and evaporated in vacuo to form 7- ethyl acetylthio-3-hydroxy-3- (4-methoxyphenyl) heptanoate (3.61 g) as an oil. NMR (CDCI3, d): 1.12 (3H, t, J = 7Hz), 1.33-1.55 (4H, m), 1.66-1.80 (2H, m), 2.30 (3H, s), 2.72-2.81 (3H, m ), 2.93 (HH, d, J = 15.5Hz), 3.80 (3H, s), 4.03 (2H, q, J = 7Hz), 4.36 (HH, s), 6.85 (2H, d, J = 9Hz), 7.30 (2H, d, J = 9Hz) Preparation 11-4) A mixture of ethyl 7-acetylthio-3-hydroxy-3- (4-methoxyphenyl) heptanoate (3.60 g) and potassium carbonate (1.40 g) in ethanol (54 ml) was stirred for 6 hours at room temperature and concentrated in vacuo. The residue was partitioned between ethyl acetate and 1% aqueous citric acid. The separated organic phase was washed with brine, dried over sodium sulfate and evaporated in vacuo to form ethyl 3-hydroxy-3- (4-methoxyphenyl) -7-mercaptoheptanoate (3.01 g) as an oil. NMR (CDC13, d): 1.12 (3H, t, J = 7.5Hz), 1.26 (ΔH, t, J = 7.5Hz), 1.35-1.60 (4H, m), 1.65-1.82 (2H, m), 2.40 -2.57 (2H, m), 2.77 (HH, d, J = 16Hz), 2.94 (HH, d, J = 16Hz), 3.60 (3H, s), 4.04 (2H, q, J = 7.5Hz), 4.36 (ÍH, s), 6.86 (2H, d, J = 9Hz), 7.30 (2H, d, J = 9Hz) Preparation 12-1) 5- (4-fluorophenyl) -2- (5-chlorovaleryl) thiophene was obtained (2.03 g) in a similar way to that of preparation 4-1). NMR (CDCI3, d): 1.79-1.99 (4H, m), 2.95 (2H, t, J = 7Hz), 3.59 (2H, t, J = 7Hz), 7.12 (2H, dd, J = 8, 8Hz) 7.59-7.68 (4H, m) Preparation 12-2) Obtained 7-chloro-3- [5- (4-fluorophenyl) -2-thienyl] • ethyl hept-2-enoate (1.71 g) (E: Z = 1: 1 mixture) in a manner similar to that of preparation 8-2). 5 NMR (CDC13, d): 1.24 (1.5H, t) 1.37 (1.5H, t), 1.63- 1.98 (4H, m), 2.56 (0.5H, t, J = 7Hz), 2.87-3.00 (1H, ), 3.08 (0.5H, t, J = 7Hz), 3.53 (HH, t, J = 7Hz), 3.61 (HH, t, J = 7Hz), 4.10-4.24 (2H, m), ^ 5.87 (0.5H, s), 6.22 (0.5H, s), 7.04-7.31 (3H, ^ TO m), 7.55-7.69 (3H, m) Preparation 12-3) Ethyl 3- (5- (4-fluorophenyl) -2-thienyl] -7-iodohept-2-enoate (1.94 g) was obtained from a similar way to that of preparation 8-3). 15 'NMR (CDCI3, d): 1.06 (1.5H, t, J = 7Hz), 1.32 (1.5H, t, J = 7Hz), 1.67-2.08 (4H, m), 3.24 (2H, t, AJ = 7Hz), 4.18 (2H, q, J = 7Hz), 6.22 (OH, s), 6.92-7.30 (4H,), 7.48-7.60 (2H, m) Preparation 12-4) 20 7-amidinothiohydrodide was obtained Ethyl-3- [5- (4-fluorophenyl) -2-thienyl] hept-2-enoate (1.57 g) in a manner similar to that of preparation 8-4). NMR (CDCI3, d): 1.05 (3H, t, J = 7Hz), 1.57-1.82 (4H, m), 3.18 (2H, t, J = 7Hz), 4.14 (2H, q, 25 J = 7Hz), 4.36 (2H, t, J = 7Hz), 6.19 (ÍH, s), 7.24-7.69 (6H,) MS (ESI +) m / z = 407 (M + H) Preparation 13-1) 4- (5-chlorovaleryl) biphenyl (1.35 g) was obtained in a manner similar to that of preparation 4-1). NMR (CDC13, d): 1.90-1.93 (4H, m), 3.06 (2H, dd, J = 6, 6Hz), 3.61 (2H, dd, J = 7, 7Hz), 7.40-7.50 (3H, m) , 7.63 (2H, d, J = 8Hz), 7.69 (2H, # d, J = 8Hz), 8.03 (2H, d, J = 8Hz). Preparation 13-2) Ethyl 3- (4-biphenylyl) -7-chlorohept-2-enoate (1 g) was obtained in a manner similar to that of Preparation 8-2). NMR (CDCI3, d): 1.10 (1.5H, dd, J = 7, 7Hz), 1.33 (1.5H, dd, J = 7, 7Hz), 1.55-1.68 (ÍH, m), 15 1.76-1.90 (ÍH, m), 2.51 (ÍH, dd, J = 7.5, 7.5Hz), 3.18 (ÍH, dd, J = 7.5, 7.5Hz), 3.52 ^ (ÍH, dd, J = 6.5, 6.5 Hz), 3.54 (ÍH, dd, J = 6.5, 6.5Hz), 4.02 (ÍH, ddd, J = 7, 7, 7Hz), 4.22 (ÍH, ddd, J = 7, 7, 7Hz), 5.92 (0.5 H, s), 6.13 20 (0.5H, s), 7.24-7.65 (9H,) Preparation 14-1) 4'-Chloro-4- (5-chlorovaleryl) biphenylyl (3.29 g) was obtained in a similar manner to that of preparation 4-1). NMR (CDCI3, d): 1.90-1.93 (4H, m), 3.05 (2H, dd, 25 J = 6, 6Hz), 3.60 (2H, dd, J = 6, 6Hz), 7.44 (2H, d, J = 8Hz), 7.56 (2H, d, J = 8Hz), 7.65 (2H, d, J = 8Hz), 8.03 (2H, d, J = 8Hz). • Preparation 14-2) 7-Chloro-3- (4'-chloro-4-biphenylyl) heppt-2-ethyl-enoate (0.70 g) was obtained in a manner similar to that of Preparation 8-2). NMR (CDC13, d): 1.11 (1.5H, dd, J = 7, 7Hz), 1.32 (1.5H, dd, J = 7, 7Hz), 1.50-1.58 (HH, m), 1.58-1.65 (HH, m), 2.49 (ÍH, dd, J = 7, 7Hz), T 3.17 (ÍH, dd, J = 7, 7Hz), 3.50 (ÍH, dd, J = 6, 6Hz), 3.54 (ÍH, dd, J = 6, 6Hz), 4.01 (HH, ddd, J = 7, 7, 7Hz), 4.22 (HH, ddd, J = 7, 7, 7Hz), 5.93 (0.5H, s), 6.12 (0.5H, s ), 7.40-7.58 (8H,) 15 Preparation 15-1) 4'-Bromo-4- (5-chlorovaleryl) biphenyl (1.97 ^^ g) was obtained in a manner similar to that of Preparation 4-1). NMR (CDCI3, d): 1.90-1.93 (4H, m), 3.05 (2H, dd, J = 7, 7Hz), 3.60 (2H, dd, J = 6, 6Hz), 7.49 20 (2H, d, J = 8Hz), 7.60 (2H, d, J = 8Hz), 7.65 (2H, d, J = 8Hz), 8.03 (2H, d, J = 8Hz). Preparation 15-2) 7-Chloro-3- (4'-bromo-4-biphenylyl) hept-2-enoate ethyl (0.64 g) was obtained in a manner similar to that of Preparation 6-2).

NMR (CDC13, d): 1.11 (1.5H, dd, J = 7, 7Hz), 1.33 (1.5H, dd, J = 7, 7Hz), 1.52-1.67 (2H, m), • 1.75-1.89 (2H, m), 2.50 (ÍH, dd, J = 7, 7Hz), 3.17 (ÍH, dd, J = 8, 8Hz), 3.51 (ÍH, dd, J = 7, 5 7Hz), 3.54 (ÍH, dd, 3 = 1, 7Hz), 4.02 (ÍH, ddd, 3 = 1, 7, 7Hz), 4.22 (ÍH, ddd, 3 = 1, 7, 7Hz), 5.93 (0.5H, s) , 6.11 (0.5H, s), 7.24-7.60 (8H, m) Preparation 16-1) ^ W 4'-Fluoro-4- (5-chlorovaleryl) biphenyl (2.95 g) was obtained in a manner similar to that of the preparation 4-1). NMR (CDC13, d): 1.89-1.95 (4H, m), 3.05 (2H, dd, 3 = 1, 7Hz), 3.60 (2H, dd, 3 = 6, 6Hz), 7.13- 7.19 (2H, m) , 7.57-7.65 (2H, m), 8.03 (2H, 15 d, J = 8.4Hz). Preparation 16-2) ^^ 7-Chloro-3- (4'-fluoro-4-biphenylyl) hept-2-enoate ethyl (1.07 g) was obtained in a manner similar to that of Preparation 8-2). 20 NMR (CDCI3, d): 1.33 (3H, dd, J = 7, 7Hz), 1.59- 1.67 (2H, m), 1.61-1.90 (2H, m), 3.17 (2H, dd, J = 7.5, 7.5 Hz), 3.54 (2H, dd, J = 7Hz), 4.22 (2H, ddd, 3 = 1, 1, 7Hz), 6.12 (ÍH, s), 7.14 (2H, dd, J = 8, 8Hz), 7.50 -7.59 (6H, m) 25 Preparation 17) Methyl 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-carboxylate (844 mg) 1,1-dioxide was obtained in a manner similar to that of the preparation 1-4). Melting point: 78-82 ° C NMR (CDC13, d): 1.44-1.80 (3H, m), 1.83-1.96 (H, m), 2.10-2.42 (2H, m), 2.72-2.85 (H, m) ), 3.14-3.78 (HH, m), 5.57 (HH, dd, 3 = 3, 8Hz), 3.82 (3H, s) MS (ESI-) m / z: 191 (MH) Preparation 18) To a solution of potassium ethyl malonate (16.1 g) in acetonitrile (4 ml) was added triethylamine (15.1 g) and magnesium chloride (11.1 g) at 0 ° C and the reaction mixture was stirred at room temperature for 2.5 hours. To the resulting aqueous suspension was added dropwise phenoxybenzoyl chloride (10.86 g) [prepared from 4-phenoxybenzoic acid (10 g) and thionyl chloride (20 ml)] for more than 15 minutes at 0 ° C and the mixture of reaction was stirred at room temperature for 5 hours. After the reaction mixture was concentrated in vacuo, toluene and 13% aqueous hydrochloric acid (60 ml) were carefully added, maintaining the temperature at less than 25 ° C. The organic layer was washed with 13% aqueous hydrochloric acid and concentrated in vacuo to form ethyl 3-oxo-3- (4-phenoxyphenyl) propanoate as a yellow oil (14 g).

NMR (CDCI3, d): 1.27 (3H, t, J = 7.0 Hz), 3.95 (2H, s), 4.24 (2H, q, J = 7.0Hz), 6.99 (2H, d, • J = 8.0Hz), 7.07 (2H, d, J = 8.0Hz), 7.18 (IH, dd, J = 8.0, 8.0Hz), 7.41 (2H, dd, J = 8.0, 5 8.0Hz), 7.92 ( 2H, d, J = 8.0Hz) MS (ESI-) m / z: 283.1 (MH) Preparation 19-1) 5-Bromo-2- (5-chlorovaleryl) thiophene (13.4 g) was obtained in a manner similar to that of preparation 4-1). W NMR (CDCI3, d): 1.86-1.91 (4H, m), 2.88 (2H, dd, J = 6.9, 6.9Hz), 3.55 (2H, dd, J = 6.66, 6.6Hz), 7.11 (1H, d , J = 4.2Hz), 7.45 (HH, d, J = 4.2Hz) Preparation 19-2) 7-Chloro-3- (5-bromo-2-thienyl) hept-2-enoate of ethyl (12.5 was obtained g) in a manner similar to that of preparation 8-2). ^ NMR (CDCI3, d): 1.22-1.59 (3H, m), 1.65-1.92 (4H, m), 3.01-3.06 (1H, m), 3.50-3.59 (2H, m), 4.10-4.23 (2H, rti), 5.85 (0.5H, s), 6.09 20 (0.5Hz, s), 6.98-7.07 (2H, m) Preparation 20-1) 7-chloro-3-hydroxy-3- (5-bromo- 2-thienyl) t-butyl heptanoate (244 g) in substantially the same manner as that of preparation 11-2). 25 NMR (CDCl 3, d): 1.36 (9H, s), 1.38-1.57 (2H, m), 1.68-1.80 (4H, m), 2.70 (HH, d, J = 15.6Hz), 2.79 (HH, d , J = 15.6Hz), 3.49 (2H, t, J = 6.9Hz), 5.00 (HH, s), 6.59 (HH, d, J = 3.9Hz), 6.89 (HH, d, J = 3.9Hz) Preparation 20-2) Tert-Butyl 7-acetylthio-3-hydroxy-3- (5-bromo-2-thienyl) heptanoate (267 g) was obtained in substantially the same manner as that of preparation 11-3). NMR (CDC13, d): 1.35 (9H, s), 1.39-1.57 (4H, m), 1.66-1.80 (2H, m), 2.31 (3H, s), 2.67 (ÍH, d, J = 15.9Hz) , 2.76 (ÍH, d, J = 15.9Hz), 2.62 (2H, t, J = 7.5Hz), 4.96 (HH, s), 6.58 (HH, d, J = 3.9Hz), 6.88 (HH, d, J = 3.9Hz) Preparation 20-3) 3-hydroxy-3- (5-bromo-2-thienyl) -7-mercaptoheptanoate of t-butyl (277 g) was obtained in substantially the same manner as that of preparation 11-4). NMR (CDCI3, d): 1.30 (ΔH, t, J = 7.8Hz), 1.31-1.39 (9H, m), 1.40-1.65 (4H, m), 1.67-1.83 (2H, m), 2.49 ( 2H, 5 dd, J = 7.8, 15Hz), 2.70 (IH, d, J = 16H), 2.79 (IH, d, J = 16Hz), 4.98 (IH, s), 6.59 (IH, d, J = 4.2 Hz), 6.89 (HH, d, J = 4.2Hz) Preparation 21-1) To a solution of 4-bromophenol (300 mg) in ketone was added potassium carbonate (264 mg) and t-butylester of bromoacetic acid (0.28). ml) at room temperature. After being stirred at the same temperature overnight, the reaction mixture was concentrated in vacuo. The resulting residue was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate and concentrated in vacuo to give 4-bromophenoxyacetic acid t-butyl ester (450 mg) as an oil. . NMR (DMSO-d6, d): 1.42 (9H, s), 4.66 (2H, s), 6.88 (2H, d, J = 4.5Hz), 7.45 (2H, d, J = 4.5Hz) Preparation 21-2 ) To a solution of 4-bromophenoxyacetic acid t-butyl ester (4 g) in dichloromethane (10 ml) was added trifluoroacetic acid (310 ml) at room temperature.

After being stirred at the same temperature for 3 hours, the reaction mixture was concentrated in vacuo. The resulting residue was diluted with ethyl acetate, washed with water and brine, dried over sodium sulfate and concentrated in vacuo to form 4-bromophenoxyacetic acid. (2.1 g) as a powder. NMR (DMSO-d6, d): 4.67 (2H, s), 6.89 (2H, d, J = 9Hz), 7.45 (2H, d, J = 9Hz) MS (ESI-): 230 (MH) Preparation 21- 3) N-ethyl-2- (4-bromophenoxy) acetamide (110 mg) was obtained in substantially the same manner as that of Example 32. NMR (DMSO-d6, d): 1.03 (3H, t, J = 7.2Hz ), 3.10- 3.19 (2H, m), 4.45 (2H, s), 6.93 (2H, d, J = 9Hz), 7.47 (2H, d, J = 9Hz), 8.11 (1H, br) Preparation 21-4 ) Cyclic pinacol ester of 4- (ethylaminocarbonylmethoxy) benzeneboronic acid (130 mg) was obtained in substantially the same manner as that of preparation 24-2). The product was used for the next reaction without further purification. Preparation 22 4- (t-Butyloxycarbonylmethoxy) benzeneboric acid (200 mg) was obtained in substantially the same manner as that of preparation 21-1). NMR (DMSO-dg, d): 1.42 (9H, s), 4.65 (2H, s), 6.84 (2H, d, J = 9.0Hz), 7.71 (2H, d, J = 9.0Hz), 7.88 (2H , s) Preparation 23-1) 4-chloro-l- (5-bromo-2-thienyl) butan-1-one was obtained (8.0 g) in substantially the same manner as that of preparation 8-1). NMR (CDC13, d): 2.21 (2H, quintet, J = 7Hz), 3.05 (2H, t, J = 7Hz), 3.66 (2H, t, J = 7Hz), 7.11 (ÍH, d, J = 4Hz) , 7.50 (HH, d, J = 4Hz) Preparation 23-2) T-butyl 6-chloro-3-hydroxy-3- (5-bromo-thienyl) hexanoate (4.46 g) was obtained in substantially the same manner as that of preparation 11-2). NMR (CDC13, d): 1.37 (9H, s), 1.64-1.80 (HH, m), 1.82-1.98 (3H, m), 2.70 (HH, d, J = 16Hz), 2.80 (HH, d, J = 6Hz), 3.48-3.55 (2H, m), 5.02 (HH, s), 6.61 (HH, d, J = 4Hz), 6.90 (HH, d, J = 4Hz) Preparation 23-3) 6- was obtained t-butyl acetylthio-3-hydroxy-3- (5-bromo-2-thienyl) hexanoate (4.77 g) in substantially the same manner as that of preparation 11-3). NMR (CDCI3, d): 1.36 (9H, s), 1.45-1.60 (HH, m), 1.62-1.94 (3H, m), 2.31 (3H, s), 2.68 (HH, d, J = 16Hz), 2.77 (HH, d, J = 16Hz), 2.85 (2H, t, J = 7Hz), 4.98 (HH, s), 6.59 (HH, d, J = 4Hz), 6.68 (HH, d, J = 4Hz) Preparation 23-4) 3-hydroxy-3- (5-bromo-2-thienyl) -6-mercaptohexanoate of t-butyl (4.0 g) was obtained in substantially the same manner as that of preparation 11-4). NMR (CDCI3, d): 1.30 (HH, t, J = 8Hz), 1.36 (9H, s), 1.44-1.62 (HH, m), 1.66-1.93 (3H, m), 2.44-2.55 (2H, m ), 2.70 (HH, d, J = 16Hz), 2.79 (HH, d, J = 16Hz), 4.99 (HH, s), 6.60 (HH, d, J = 4Hz), 6.99 (HH, d, J = 4Hz) Preparation 24-1) A mixture of 4-bromobenzaldehyde (5.00 g), 5-tosymethyl isocyanide (5.43 g) and potassium carbonate (5.60 g) in methanol (50 ml) was refluxed for 2 hours and concentrated. The residue was obstructed between ethyl acetate and saturated aqueous ammonium hydrochloride. The layer ^ separated organic was washed with water and brine, dried Sodium sulfate and filtered. The filtrate was treated with silica gel and the residue obtained was triturated with n-hexane to form 5- (4-bromophenyl) oxazole (4.06 g) as a solid. NMR (CDC13, d): 7.37 (OH, s), 7.51-7.58 (4H, m), 15 7.93 (OH, s) MS (ESI +): 224 (M + H) ^^ Preparation 24-2) A mixture of 5- (4-bromophenyl) oxazole (672 mg), bis (pinacolato) diborane (762 mg), dichlorobis (triphenyl-20-phosphine) of palladium (II) (42.1 mg) and potassium acetate (883 mg) in dioxane (15 ml) was stirred for 14 hours at 80 ° C to form cyclic pinacol ester of 4- (5-oxazolyl) benzeneboronic acid. After cooling to room temperature, the mixture was used in the next reaction without 25 a later purification.

Preparation 25 (4- (Methoxycarbonylaminomethyl) phenyl) boronic acid (70 mg) was obtained from (4-aminomethylphenyl) boric acid hydrochloride in a manner similar to that of Example 130. NMR (DMSO-d6, d): 3.53 (3H, s), 4.18 (2H, d, J = 7.5Hz), 7.20 (2H, d, J = 8.5Hz), 7.66-7.75 (3H, m), 8.00 (2H, s) Preparation 26 (4- (Cyclopropylcarbonyloxy) phenyl) boronic acid (77 mg) was obtained from (4-hydroxyphenyl) boric acid in a manner similar to that of Preparation 21-1). NMR (DMSO-ds, d): 1.00-1.07 (4H,), 1.85-1.94 (HH, m), 7.08 (2H, d, J = 8.5Hz), 7.91 (2H, d, J = 8.5Hz), 8.09 (22H, s) Preparation 27 (4- (Ethoxycarbonylmethoxy) phenyl) boronic acid (100 mg) was obtained in a manner similar to that of preparation 21. NMR (DMSO-d6, d): 1.21 (3H, dd, J = 7.2, 7.2Hz), 4.17 (2H, ddd, J = 7.2, 7.2, 7.2Hz), 4.78 (2H, s), 6.87 (2H, d, J = 8.5Hz), 7.72 (2H, d, J = 8.5Hz), 7.88 (2H, s) Preparation 28 (4- (Ethylcarbonylmethoxy) phenyl) boric acid (95 mg) was obtained in a manner similar to that of Preparation 21-1).

NMR (DMSO-d6, d): 0.97 (3H, dd, J = 7.2, 7.2Hz), 2.49-2.54 (2H, m), 4.82 (2H, s), 6.84 (2H, d, J = 8.5Hz) , 7.71 (2H, d, J = 8.5Hz), 7.67 (2H, s) Preparation 29 (4-Cyclopropylaminocarbonyl-methoxyphenyl) boric acid (160 mg) was obtained in a manner similar to that of Example 32. NMR (DMSO- d6, d): 0.46-0.50 (2H, m), 0.61-0.64 (2H, m), 2.65-2.72 (HH, m), 4.43 (2H, s), 6.88 (2H, d, J = 8.5Hz) , 7.72 (2H, d, J = 8.5Hz), 7.88 (2H, s), 8.13 (1H, br) Preparation 30 To a solution of (2S) -2- (5-bromo-2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid 1,1-dioxide (4.24 g) in N , N-dimethylformamide (60 ml) was added 1-hydroxybenzotriazole (1.62 g) and diisopropylcarbodiimide (1.88 ml) at room temperature. After 1 minute, the solution was added to hydroxylamine trityl (a) 5 (14.4 μmol / crown x 100) hydroxylamine rings, the reaction mixture was allowed to stand overnight at room temperature. The crowns were successively washed with N, N-dimethylformamide, methanol and dichloromethane, and air dried to form ^. (2S) -N- [2- [2- (5-Bromo-2-thienyl) -1,1-dioxo-10-3,4,5,6-tetrahydro-2H-thiopyran-2-yl] -acetyl) ] -hydroxylamine trityl (b) (10.0 μmol / crown x 100). Preparation 31-1) To a suspension of 3-nitrophenylboronic acid (2.33 g) and tetrakis (triphenylphosphine) palladium (1.29 g) in degassed N, N-15 dimethylformamide (50 ml) was added a solution of sodium carbonate (8.5 g. ) in water ^ degassed (20 ml) and (2S) -N- [2- (2- (5-bromo-2-thienyl) -1, l-dioxo-3,4,5,6-tetrahydro-2H-thiopyran crowns -2-yl] acetyl) hydroxylaminetrityl (202 μmol, 10.1 μmol / crown x 20 20) in a nitrogen atmosphere. After heating the resulting mixture for 48 hours at 60 ° C, the crowns were washed successively with degassed N, N-dimethylformamide, a solution of sodium diethyldithiocarbamate (1.0 g) and diisopropylethylamine (1.0 ml) in N, N-dimethylformamide ( 200 ml), N, N-dimethyl ormamide, methylsulfoxide, water, methanol and dichloromethane, to form (2S) -N- [2- [2- (5- (3-nitrofenyl) -2-thienyl) - 1, 1-dioxo-3, 4, 5, 6-tetrahydro-2H-thiopyran-2-yl] acetyl] hydroxylaminetrityl (202 μmol, 10.1 μmol / crown x 20).

Preparation 31-2) To a solution of tin (II) dihydrate chloride (7.67 g) in N, N-dimethylformamide (17 ml) were added (2S) -N- [2- (2- (5- (3-nitrofenyl) -2-thienyl) -1,1-dioxo-3,4,5,6-tetrahydro-2 H-thiopyran-2-yl) acetyl] hydroxylamine trityl (304 μmol, 13.2 μmol / crown x 23). The reaction mixture was allowed to stand overnight at room temperature. The crowns were washed successively with N, N-dimethylformamide, water, methanol and dichloromethane, and air-dried to form (2 S) -N- [2- [2- (5- (3-aminophenyl) -2) -N -thienyl) -1, l-dioxo-3, 4, 5, 6-tetrahydro-2 H-thiopyran-2-yl] acetyl] hydroxylaminetrityl (13.2 μmol / crown x 23). The following compounds were obtained from 6-methyl-3 (trifluoromethanesulfonyloxy) pyridine in a manner similar to that of Preparation 24-2). Preparation 32 Cyclic 6-methylpyridine-3-boronic acid esterpinacol Preparation 33 Cyclic 6-methoxypyridine-3-boronic acid esterpinol Preparation 34 Cyclic 4- (5-methyl-1,2,4-oxadiazol-3-yl) cyclic acid ester ) Benzeneric Preparation 35 Cyclic 5- (methoxycarbonylamino) pyridine-3-boric acid esterpinacol Preparation 36 1, 1-(2S) -N- (2-tetrahydropyranyloxy) -2- (5- (pinacolatoboryl) 2-thienyl] dioxide] 3, 4, 5, 6-tetrahydro-2 H-thiopyran-2-acetamide Preparation 37 4- (Methylaminocarbonylmethyl) benzeneboric acid cyclic esterpinacol Preparation 38 Cyclic 2- (methylaminocarbonyl) benzofuran-5-boronic acid cyclic esterpinacol Example 1 Diisopropylamide 1.5M lithium monotetrahydrofuran in cyclohexane (0.28 ml) was added dropwise to a stirred suspension of 2- [4- (4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H 1,1-dioxide. -thiopyran (117 mg) in tetrahydrofuran (2.4 ml) under cooling with dry ice-acetone and an atm Nitrogen sphere, and the mixture was stirred under the same conditions for 15 minutes, then a solution of t-butylbromoacetate (75 mg) in tetrahydrofuran (0.2 ml) was added dropwise and the resulting mixture was stirred under the same conditions for 2 hours. A saturated aqueous solution of ammonium chloride was added to the stirred reaction mixture and the resulting mixture was extracted with diethyl ether. The extract was washed with brine, dried over sodium sulfate, and evaporated in vacuo. The residue was chromatographed (eluent: toluene-ethyl acetate) on silica gel to obtain a mixture (86 mg) of 1,1-d-oxide of 2- [4- (4-chlorophenoxy) phenyl] -3,4 , 5, 6-tetrahydro-2H-t? Op? Aran-2-t-butyl acetate and the starting material. A solution of trifluoroacetic acid (560 mg) and the mixture obtained (79 mg) in dichloromethane (3.0 ml) was allowed to stand at room temperature for 3 days and evaporated in vacuo. The residue was dissolved in ethyl acetate and extracted five times with a saturated aqueous solution of sodium bicarbonate. The aqueous extracts were combined, acidified with hydrochloric acid, and extracted with ethyl acetate. The organic extract was washed with brine, dried over sodium sulfate, and evaporated in vacuo to obtain 1,1-d-oxido of 2- [4- (4-chlorophenoxy?) Phenol] -3 , 4,5,6-tetrahydro-2H-t? Op? Aran-2-acetic (44 mg) as a colorless powder. Melting point: 191-193 ° C IR (KBr): 1711, 1290, 1244, 1124 crn "1 NMR (CDCI3, d): 1.75-2.05 (2H, m), 2.15 (2H, m), 2.62.85 (2H, m), 3.08-3.15 (2H, m), 3.21 (IH, d, J = 15.6Hz), 3.60 (IH, d, J = 15.6Hz), 6.94-7.01 (4H, m), 7.31 ( 2H, dd, J = 6.7, 5 2.1Hz), 7.59 (2H, d, J = 9.0Hz) (-) API-ES MS m / z: 393 (M + -H) Anal heat, for C1? HX9C105S: C 57.79, H 4.85 Found: C 57.88, H 4.83 ^^ Example 2 10 A mixture of ethyl 2- (4-methoxyphenyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetate (100 mg) and lithium hydroxide monohydrate (42.8 mg) in a mixture of methanol and water was stirred for 4 hours at 60 [deg.] C. After cooling to room temperature, the mixture was acidified with acid Hydrochloric acid 4N and concentrated in vacuo. The residue was partitioned between ethyl acetate and IN hydrochloric acid. The ^^ separated organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuo to form 2- (4-methoxyphenyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid. 20 (93 mg) as a crystalline solid. NMR (DMSO-d6, d): 1.44-1.80 (4H, m), 2.26-2.54 (3H, m), 2.62-2.79 (2H,), 3.00 (ÍH, d, J = 14.5Hz), 3.75 (3H , s), 6.89 (2H, d, J = 9Hz), 7.48 (2H, d, J = 9Hz) 25 MS (ESI-) m / z: 265 (MH) ETemplo 3 To a solution of ethyl 2- [5 - (4-fluorophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-t? Opran-2-acetate (315 mg) in methanol (4 ml) was added an aqueous solution from Sodium hydroxide IN (1.3 ml) at 0 ° C and the mixture was stirred for 5 hours at room temperature. The resulting mixture was evaporated to remove methanol. The residue was acidified with IN hydrochloric acid (HCl) and extracted ^^ with ethyl acetate (x3). The combined organic layer is 10 washed with brine, dried over magnesium sulfate and concentrated to form 2- [5- (4-fluorophenyl) -2-t? In? L] - 3, 4, 5, 6-tetrahydro-2H acid -t? op-2-acetic acid (296 mg) as a white solid. NMR (CDC13, d): 1.58-1.92 (4H, m), 2.20-2.32 (HH, 15 m), 7.57-2.68 (2H, m), 2.70-2.81 (HH, m), 2.89 (HH, d, J = 14Hz), 2.97 (ÍH, d, J = 14Hz), 6.97-7.08 ^ (4H,), 7.48-7.56 (2H, m) MS (ESI-) m / z: 335 (MH) Example 4 20 A a 1,1-d? oxido solution of methyl 2- (4-phenoxybenzyl) -3,4,5,6-tetrahydro-2H-t? op? aran-2-carboxylate in methanol ( MeOH) (5 ml) was added a solution of lithium hydroxide monohydrate (375 mg) in water (H20) (5 ml) at room temperature. After being stirred at 60 ° C for 2 25 hours, the mixture was concentrated in vacuo to remove the MeOH. The residual solution was acidified with IN hydrochloric acid and extracted with ethyl acetate (AcOEt) (20 ml x 2). The combined extract was washed with brine, dried over magnesium sulfate, and concentrated in vacuo to form 2- (4-phenoxybenzyl) -3,4,5,6-tetrahydro-2H- 1,1-dioxide. Thiopyran-2-carboxylic acid (320 mg) as an amorphous powder. NMR (CDC13, d): 1.70-1.84 (2H, m), 1.95-2.20 (3H, m), 2.25-2.37 (HH, m), 3.11-3.25 (3H, m), 3.16 m (HH, d, J = 14Hz), 6.91 (2H, d, J = 8Hz), 7.00 (2H, d, J = 8Hz), 7.11 (ÍH, t, J = 8Hz), 7.20 (2H, d, J = 8Hz), 7.33 (2H, t, J = 8Hz) MS (ESI-) m / z: 359 (MH) Example 5 15 2- (4-phenoxybenzyl) -3,4,5,6-tetrahydro-2H-thiopyran- 2-carboxylic acid (280 mg) in a manner similar to that of Example 4. NMR (CDCl 3, d): 1.45-2.02 (5H, m), 2.35-2.46 (HH, m), 2.52-2.65 (HH, m), 2.68-2.85 (ÍH, m), 3.07 20 (2H, dd, J = 3, 14Hz), 6.90 (2H, d, J = 8Hz), 6.99 (2H, d, J = 8Hz), 7.09 (ÍH, t, J = 8Hz), 7.13 (2H, d, J = 8Hz), 7.32 (2H, t, J = 8Hz) MS (ESI-) m / z: 327 (MH) Example 6 25 To a solution of ethyl 2- (4-phenoxyphenyl) -1, 3- dithian-2-acetate (370 mg) in ethanol (4 ml) was added an aqueous solution of IN sodium hydroxide (2 ml) and the mixture was stirred at 50 ° C for 3 hours. The resulting mixture was evaporated to remove the ethanol. The residue was acidified with 1N HCl and extracted with diethyl ether. The organic layer was washed with brine, and dried over magnesium sulfate. The solvent was evaporated to form 2- (4-phenoxyphenyl) -1,3-dithiane-2-acetic acid (280 mg) as a white crystal. NMR (CDC13, d): 2.03 (2H, br), 2.83 (4H, br), i? 3.22 (2H, br), 6.93-7.05 (4H, m), 7.13 (ÍH, d, J = 7.0Hz), 7.41-7.48 (12H,), 7.82-7.86 (2H, m) MS (ESI-) m / z: 345.1 (MH) Example 7 15 A 1.5M lithium monotetrahydrofuran diisopropylamide solution in cyclohexane (1.60 ml) was added dropwise ^^ to a stirred solution of 2- [4- (4-chlorophenoxy) phenyl] -2,3,4,5-tetrahydrothiophene 1,1-dioxide (646 mg) in tetrahydrofuran (6.5 ml) under a nitrogen atmosphere 20 and cooling with dry ice-acetone, and the resulting solution was stirred under the same conditions for 35 minutes. A solution of allyl bromide (532 mg) in tetrahydrofuran (1.9 ml) was added dropwise and the resulting mixture was stirred under the same conditions for 1 hour and 30 minutes. After adding a saturated aqueous solution of ammonium chloride (10 ml) under the same conditions, the reaction mixture was extracted with ethyl acetate. The extract was washed successively with hydrochloric acid and a saturated aqueous solution of sodium bicarbonate, dried over magnesium sulfate, and evaporated in vacuo to obtain an oil (0.68 g). Potassium permanganate was added successively (259 mg), sodium periodate (1.75 g), and potassium carbonate (618 mg) to a stirred emulsion of the oil obtained in tertiary butyl alcohol (22 ml) and water (38 ml) at room temperature and the resulting mixture stirred at the same temperature for 1 hour and 40 minutes. The reaction mixture was acidified to pH 1.0 approx. with IN hydrochloric acid (10 ml) under ice-cooling, and then sodium bisulfite was added portion wise under the same condition, until the mixture turned yellow. This yellow mixture was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium bisulfite and brine, dried over sodium sulfate, and evaporated in vacuo. The powdery residue was washed with a mixture of dnsopropyl ether diethyl ether to obtain a colorless powder (401 mg), of which 388 mg (eluent: toluene-ethyl acetate-acetic acid) was chromatographed on silica gel to obtain a oil. The obtained oil was pulverized from n-hexane to obtain 1,1-d? Oxido of 2- [4- (4-chlorophenoxy) phenyl] -2,3,4,5,5-tetrahydrothiophen-2-acetic acid (306 mg) as a colorless amorphous powder. Melting point: 45-50 ° C IR (KBr): 2750-2400, 1734, 1716, 1300, 1244, 5 1126 cm "1 NMR (DMSO-dg, d): 2.16-2.25 (2H, m), 2.65 -2.77 (2H, m), 3.08 - 3.41 (4H, m), 7.00-7.10 (4H, m), 7.41-7.51 (4H, m), 12.38 (HH, br) (-) API-ES MS m / z: 379 and 381 (M + -H)] W Anal cale, for CXyH17Cl05S: C 56.76, H 4.50 Found: C 57.32, H 5.04 Example 8 Potassium permanganate (172 mg), sodium periodate (1.28 g) , and potassium carbonate (409 mg) were added 15 successively to a stirred emulsion of 2-allyl-2- [4- (4-chloro-phenoxy) -phenyl] -3,4,5,6-tetrahydro-2H-α-thiopyran 1,1-dioxide (372 mg ) in tertiary butyl alcohol (15 ml) and water (26 ml) at room temperature, and the resulting mixture was stirred at the same temperature for 1 hour and 30 minutes. 20 minutes. The reaction mixture was acidified to pH 1.0 approx. with concentrated hydrochloric acid under cooling with ice, and then sodium bisulfite was added portion wise under the same condition until the mixture turned yellow. This yellow mixture was extracted with acetate Ethyl. The extract was washed with brine, dried over sodium sulfate, and evaporated in vacuo. The residue was chromatographed (eluent: toluene-ethyl acetate-acetic acid) on silica gel to obtain a colorless powder (277 mg), which was washed with n-hexane to obtain 1,1-dioxide of 2- acid [ 4- (4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid (250 mg) as a colorless powder. Melting point: 191-193 ° C Example 9 ^^ 1,1- [4- (4-chlorophenoxy) phenyl] -3-acid dioxide, 10 4, 5, 6-tetrahydro-6-methyl-2H-thiopyran-2-acetic acid (59 mg) was prepared in a manner similar to that of Example 8. IR (KBr): 3442, 1735, 1714, 1284, 1245 , 1124 crtf1 NMR (DMSO-ds, d): 1.16 (3H, d, J = 6.6Hz), 1.62- 1.98 (4H, m), 2.47-2.63 (2H,), 3.2-3.59 15 (3H, m) , 6.98-7.10 (4H, m), 7.46 (2H, d, J = 9.0Hz), 7.55 (2H, J = 9.0Hz) ^ (-) API-ES MS m / z: 407 and 409 (M + -H Example 10 A suspension of 1,1-dioxide of (2R or 2S) -2- [4- (4-20 chlorophenoxy) -phenyl] -3,4,5,6-tetrahydro-N- ((1R) - 1- phenylethyl) -2H-thiopyran-2-acetamide (diastereomer A, 149 mg) obtained in Example 31 in a mixture of 14N sulfuric acid (7.0 ml) and 1,4-dioxane (4.2 ml) was stirred at reflux for 21 hours and cooled to room temperature. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water and brine (twice), dried over magnesium sulfate, and evaporated in vacuo. The residue was chromatographed (eluent: dichloromethane-methanol) on silica gel to obtain (2R or 2S) - (-) -2- [4- (4-chlorophenoxy) -phenyl] -3-1,1-dioxide, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetic acid (an optical isomer A, 109 mg) as a crude brown gum. IR (KBr): 1734, 1716, 1284, 1244, 1122 cm "1 NMR (CDC13, d): 1.93 (2H, m), 2.14 (2H, m), 2.6- 2.85 (2H, m), 3.08-3.16 (2H, m), 3.22 (HH, d, J = 15.6Hz), 3.62 (HH, d, J = 15.6Hz), 6.95- 7.04 (4H, m), 7.28-7.35 (2H, m), 7.60 ( 2H, d, J = 9.0Hz) (-) API-ES MS m / z: 393 and 395 (M + -H) w 2"5 D: -32.3 ° (C = 1.0, MeOH HPLC chiral anal: column: Chiralpak AS (4.6 x 250 mm, Daicel Chemical Industries, Ltd.) eluent: n-hexane-ethanol-TFA (700: 300: 1) circulation rate: 1.0 ml / minute detection: 220 nm retention time: 50.0 minutes Example 11 (2R or 2S) -2- [- (4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid 1,1-dioxide (an optical isomer B , 77 mg) was prepared from 1,1-dioxide of (2R or 2S) - (+) -2- [4- (4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-N- ((IR) -1-phenylethyl) -2H-thiopyran-2-acetamide (diastereomer B, 133 mg) obtained in Example 31 in a manner similar to that of Example 10. IR (KBr): 1711, 1290, 1242 , 1122 cm "1 NMR (CDC13, d): 1.82-1.95 (2H, m), 2.10-2.15 (2H, m), 2.62-2.80 (2H, m), 3.03-3.11 (2H, m), 3.21 ( ÍH, d, J = 15.6Hz) , 3.60 (ÍH, d, J = 15.6Hz), 6.92-7.01 (4H, m), 7.28-7.34 (2H, m), 7.59 (2H, d, J = 9.0Hz) (-) API-ES MS / z: 393 (M + -H) Anal chiral HPLC: column: Chiralpak AS (4.6 x 250 mm, Daicel 15 Chemical Industries, Ltd.) eluent: n-hexane-ethanol-TFA (700: 300: 1) ^^ circulation speed: 1.0 ml / minute detection: 220 nm retention time: 8.96 minutes 20 Example 12 To a solution of 2- [4- (4-chlorophenoxy) phenyl] 1,1-dioxide] -3, 4, 5 , 6-tetrahydro-2H-thiopyran-2-acetic acid (16.8 g) in ethyl acetate (420 ml) was added (R) - (+) - amethybenzylamine (2.84 g) at room temperature. After stirring overnight at the same temperature, the resulting crystal was filtered and washed with ethyl acetate to form acid salt of (R) - (+) -a-methylbenzylamine of 1,1-dioxide acid (2R or 2S) -2- [4- (4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic (9.43 g). A suspension of the resulting salt in ethyl acetate (200 ml) was washed with IN hydrochloric acid (100 ml x 2), water and brine, and concentrated to form the free acid. This procedure was repeated three times (second: amine 0.75 eq; third: 0.85 eq) to form the optically resolved acid of (2R or 2S) - (-) -2- [4- (4-chlorophenoxy) phenyl] - 3,4,5,6-tetrahydro-2H-thiopyran-2 -acetic (an optical isomer A) (4.75 g) as a white solid. w ": -32.3 ° (C = 1.0, MeOH) 15 Optical purity: 91% ee Chiral anal HPLC: ^^ column: Chiralpak AS (4.6 x 250 mm, Daicel Chemical Industries, Ltd.) eluent: n- hexane-ethanol-TFA (700: 300: 1) 20 speed of circulation: 1.0 ml / minute detection: 220 nm retention time: 50.0 minutes Example 13 To a solution of 1,1-dioxide of 2- (5-bromo) acid -2- 5 thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid (1 g) in ethanol (8 ml) was added (R) - (+) - -methylbenzylamine (185 mg) At room temperature, after being stirred overnight at room temperature, the resulting crystal was filtered and washed with ethanol to form a (R) - (+) - Cy-methylbenzylamine salt of acid 1,1-dioxide. - (5-Bromo-2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid A suspension of the resulting salt in ethyl acetate was washed with IN hydrochloric acid and brine, and concentrated to form the free acid.This procedure was repeated twice to form the optical acid solved by (2R or 2S) -2- (5-bromo-2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic 1,1-dioxide (300 mg) as a solid white. NMR (DMS0-d6, d): 1.74-1.87 (4H, m), 2.30-2.37 (HH, m), 3.07-3.56 (5H, m), 7.02 (HH, d, J = 4.2Hz), 7.21 ( ÍH, d, J = 4.2Hz) MS (ESI-) m / z: 351 (MH) w ": -25.3 ° (C = 1.0, MeOH) Optical purity: 95% ee Chiral anal HPLC: column: Chiralpak AS (4.6 x 250 mm, Daicel Chemical Industries, Ltd.) eluent: n-hexane-ethanol-acid trifluoroacetic (TFA) (700: 300: 1) circulation speed: 1.0 ml / minute detection: 220 nm retention time: 20.2 minutes Example 14 5 A mixture of 1,1-dioxide of acid 2- [4- (4- chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid (98.7 mg), ammonium formate (78.8 mg), and carbon on 10% palladium (50% moisture, 60 mg ) in ethanol (5 ^ * ml) was stirred at reflux for 3 hours and 20 minutes, and 10 filtered. The filtrate was evaporated in vacuo and the residue was partitioned between ethyl acetate and 0.1N hydrochloric acid. The organic layer was washed with brine, dried over sodium sulfate, and evaporated in vacuo. The residue was pulverized from diisopropyl ether to obtain 1,1-dioxide 3, 4, 5, 6-tetrahydro-2- (4-phenoxyphenyl) -2H-thiopyran-2-acetic acid (87 mg) as a colorless powder. At Melting point: 208.5-209.5 ° C IR (KBr): 2750-2550, 1707, 1290, 1246, 1124 crn "1 NMR (CDC13, d): 1.75-2.25 (4H,), 2.74 (2H, m) , 20 3.11 (2H, m), 3.21 (HH, d, J = 15.6Hz), 3.61 (HH, d, J = 15.6Hz), 6.97-7.07 (4H, m), 7.14 (HH, t, J = 7.4Hz), 7.36 (2H, t, J = 7.7Hz), 7.59 (2H, d, J = 9.0Hz) (-) API-ES MS m / z: 359 (M + -H) 5 Example 15 A solution of Oxalyl chloride (76.2 mg) in dichloromethane (0.7 ml) was added dropwise to a stirred suspension of 1,1-d? oxido of 2- [4- (4-chlorophenoxy) phenyl] -3,4 acid, 5,6-tetrahydro-2H-t? Op? A-2-acetic acid (118 mg) and N, N? -methylformamide (1.10 mg) in dichloromethane (1.2 ml) under ice-cooling and a nitrogen atmosphere, then the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours and evaporated in vacuo.The residue was dissolved in dichloromethane (1.6 ml) and the solution was added dropwise to a stirred mixture of Ammonium hydroxyl chloride (125 mg), an aqueous solution of sodium hydroxide IN (1.8 ml), tetrahydrofuran (3.6 ml), and tertiary butyl alcohol (1.8 ml) at room temperature and the resulting mixture was stirred at room temperature for 2 hours and 30 minutes. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was separated, dried over sodium sulfate, and evaporated in vacuo. The residue was chromatographed (eluant: toluene-ethyl acetate-acetic acid) on silica gel (2.6 g) to obtain a colorless powder, which was washed with dusopropyl ether to obtain 1,1-d? oxide of 2- [4- ( 4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-Nh? Drox? -2H-t? Op? Ran-2-acetam? Da (88 mg) as a colorless powder. Melting point: 179-180 ° C (dec.) IR (KBr): 3421, 3315, 3220, 1652, 1284, 1248, 1119 cm "1 NMR (DMSO-dg, d): 1.74-1.99 (4H, m), 2.5 (ÍH, m), 2.87 (ÍH, br d, J = 13Hz), 3.01-3.55 ( 4H, m), 6.87-7.12, (4H, m), 7.42-7.59 (4H, m), 8.73 (H, s), 10.48 (H, s) (+) API-ES MS m / z: 432 ( M ++ Na) Anal cale, for Cx5H2oClN05S: C 55.68, H 4.92, N 3.42 Found: C 55.67, H 5.28, N 3.23 Example 16 A solution of oxalyl chloride (55.8 mg) in dichloromethane (0.5 ml) was added dropwise to a stirred solution of crude acid 1,1-dioxide (2R or 2S) - (4- (4-chlorophenoxy) phenyl) 3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid (a optical isomer A, 87 mg) obtained in Example 12 and N, N-dimethylformamide (0.80 mg) in dichloromethane (0.88 ml) under cooling with ice and a nitrogen atmosphere, then the resulting mixture was stirred at room temperature under an atmosphere of nitrogen for 2 hours and 30 minutes, and evaporated in vacuo, the residue was dissolved in dichloromethane (0.9 ml) and the solution was added dropwise to the stirred mixture of Ammonium idroxilchloride (91.7 mg), an aqueous solution of IN sodium hydroxide (1.3 ml), tetrahydrofuran (22.6 ml), and tertiary butyl alcohol (1.3 ml) at room temperature and the resulting mixture was stirred at the same temperature for 1 hour. hour and 30 minutes.

The reaction mixture was partitioned between water and ethyl acetate. The organic layer was separated, dried over sodium sulfate, and evaporated in vacuo. The residue was chromatographed (eluant: toluene-ethyl acetate-acetic acid) on silica gel (1.9 g) to obtain a pale brown powder (67 mg), which was washed with dnsopropyl ether to obtain 1,1-d? oxide of (R or S) - (-) -2- [4- (4-chlorophenoxy) phenyl] -3, 4, 5, 6-tetrahydro-Nh? drox? -2H-t? op? ran-2 -acetamide (optical isomer A, 55 mg) as a colorless powder. Melting point: 183.5-187 ° C (dec.) W2J: -9.3 ° (C = 0.71, MeOH) IR (KBr): 3446, 3423, 1653, 1284, 1250, 1119 crn "1 NMR (DMSO-ds, d): 1.75-2.05 (4H, m), 2.5 (ÍH, m), 2.87 (ÍH, br d, J = 12.9Hz), 3.01-3.5 (4H, m), 7.00 (2H, d, J = 8.9Hz), 7.08 (2H, d, J = 8.9Hz ), 7.46 (2H, d, J = 8.9Hz), 7.56 (2H, d, J = 8.9Hz), 8.73 (IH, s), 10.48 (IH, s) (+) API-ES MS m / z: 432 and 434 (M ++ Na) (-) API-ES MS m / z: 408 and 410 (M + -H) Analogous chiral HPLC: column: Chiralpak AS (4.6 x 250 mm., Daicel Chemical Industries, Ltd. ) eluent: n-hexane-ethanol-TFA (700: 300: 1) circulation speed: 1.0 ml / minute detection: 220 nm retention time: 18.2 minutes E? emplo 17 1,1-d? óx? do de ( R or S) - (+) -2- [4- (4-chlorophenoxy) phenyl] -3, 4, 5, 6-tetrahydro-Nh? Drox? -2H-t? Op? Ran-2-acetam Da (41 mg) was prepared from 1,1-d-oxido of crude acid (2R or 2S) -2- [4- (4-chlorophenoxy) phenyl] -3,, 5, 6-tetrahydro -2H-t? Op-2-acetic acid (an optical isomer B, 87 mg) obtained in Example 11 in a manner similar to that of Example 16.

Melting point: 187-188 ° C (dec.) M2: 10.5 ° (C = 0.56, MeOH) IR (KBr): 3444, 3423, 3317, 3224, 1655, 1284, 1250, 1122 crn "1 NMR (DMS0-d6, d): 1.75-2.05 (4H, m ), 2.5 (HH, m), 2.87 (1H, br d, J = 13.6Hz), 3.01-3.52 (4H, m), 7.00 (2H, d, J = 8Hz), 7.08 (2H, d, J = 8.9Hz), 7.46 (2H, d, J = 8.9Hz), 7.56 (2H, d, J = 8.9 z), 8.73 (IH, s) 10.48 (IH, s); +) API-ES MS m / z 432 and 434 (M ++ Na);-) API-ES MS m / z 408 and 410 (M + -H) Anal Chiral HPLC, column: Chiralpak ASS (4.6 x 250 mm, Daicel Chemical Industries, Ltd.) eluent: n-hexane-ethanol-TFA (700: 300: 1) circulation speed: 1.0 ml / minute detection: 220 nm retention time: 27.9 minutes Example 18 2- (4- (4-chlorophenoxy) 1,1-dioxide) phenyl] -3,4,5,6-tetrahydro-N-hydroxy-6-methyl-2H-thiopyran-2-acetamide (30 mg) was prepared from 2- [4- (2- ( 4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-6-methyl-2H-thiopyran-2-acetic acid (55 mg) in a manner similar to that of Example 15. Melting point: 102 ° C ( dec.) IR (KBr): 3446 and 3421 (br), 1668, 1282, 1246, 1124 cm "1 NMR (DMSO-d6, d): 1.17 (3H, d, J = 6.6Hz), 1.5- 2.05 (4H,), 2.4 (HI, m), 2.8-2.95 ( ÍH, br d), 3.09 (1H, d, J = 15.0Hz), 3.23 (IH, d, J = 15.0Hz), 3.54 (IH, 7.00 (2H, d, J = 8.8Hz), 7.08 (2H, d, J = 8.9Hz), 7.42-7.49 (2H, m), 7.56 (2H, d, J = 8.9Hz), 8.73 (H, s), 10.49 (H, 3) (+) API-ES MS / z: 446 and 448 (M + + Na) Example 19: 3, 4, 5, 6-tetrahydro-N-hydroxy-2- (4-phenoxyphenyl) -2H-thiopyran-2-acetamide 1,1-dioxide ( 41 mg) was prepared from 3, 4, 5, 6,6-tetrahydro-2- (4-phenoxyphenyl) -2H-thiopyran-2-acetic acid 1,1-dioxide (66 mg) in a manner similar to of Example 15. Melting point: 182-183 ° C (dec.) IR (KBr): 3446 and 3423 (br), 1655, 1288, 1246, 1115 cm "1 NMR (DMSO-d6, d): 1.75- 2.05 (4H, m), 2.4 (HH, m), 2.87 (HH, br d, 3 = 13.0Hz), 3.04-3.55 (4H, m), 6.96 (2H, d, J = 8.9Hz), 7.06 ( 2H, d, J = 7.5Hz), 7.19 (ÍH, t, J = 7.3Hz), 7.43 (2H, t, J = 7.4Hz), 7.54 (2H, d, J = 8.9Hz), 8.74 (ÍH, s), 10.48 (HH, s) (+) APCl MS m / z: 376 (M + + H), 343 (M + -NHOH) (-) API-ES MS m / z: 374 (M + -H) Example 20 2- [4- (4-chlorophenoxy) phenyl] 1,1-dioxide] -2, 3, 4, 5-tetrahydro-N-hydroxy-2-thiophene-2-acetamide (88 mg) was prepared from 2- [4- (4-chlorophenoxy) phenyl 1,1-dioxide] -2, 3, 4, -tetrahydrothiophen-2-acetic acid (122 mg) in a manner similar to that of Example 15. Melting point: 63-68 ° C (dec.) IR (KBr): 3423 (br), 1662, 1296, 1244, 1126 atf1 NMR (DMS0-d6, d): 2.19-2.23 (2H, m), 2.56-3.28 (6H, m), 6.99-7.10 (4H,), 7.38-7.48 (4H , m), 8.73 (HH, s), 10.40 (HH, s) (+) APCl MS m / z: 396 and 398 (M ++ H), 363 and 365 (M + -NHOH) Cale. anal, for C18H18C1N05S: C 54.61, H 4.58, N 3.54 Found: C 55.20, H 5.06, N 3.26 Example 21 To a solution of potassium hydroxide (400 g) in water (200 ml) was added a solution of ethyl 7-amidinothio-3- [4- (4-chlorophenoxy) phenyl] hept-2-enoate hydrochloride. (70.1 g) in tetrahydrofuran (100 ml), and the mixture was refluxed overnight, after the solution was cooled and acidified with IN HCl, the mixture was extracted with ethyl acetate (100 ml x 3) . The combined organic layer was washed with water and brine, dried over magnesium sulfate and concentrated under reduced pressure to form 2- [4- (-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H- acid. thiopyran-2-acetic (60 g) as a yellow oil. NMR (CDC13, d): 1.51-1.90 (4H, m), 2.26-2.38 (HH, m), 2.48-2.68 (3H, m), 2.90 (2H, d, J = 14Hz), 2.98 (2H, d) , J = 14Hz), 6.94 (4H, d, J = 8Hz), 7.27 (2H, d, J = 8Hz), 7.57 (2H, d, J = 8Hz) MS (ES-) m / z: 361 (MH Example 22 2- [4- (4-Bromophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid (3.99 g) was obtained in a manner similar to that of Example 21.

NMR (CDCI3, d): 1.50-1.87 (4H, m), 2.27-2.49 (HH, m), 2.47-2.70 (3H, m), 2.90 (HH, d, J = 15Hz), 3.00 (HH) , d, J = 15Hz), 6.96 (4H, d, J = 9Hz), 7.44 (4H, d, J = 9Hz) MS (ESI-) m / z: 407 (NH) Example 23 2- [5 - (4-fluorophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-ethyl acetate (117 mg) from 7-amidinothio-3- [5- ( 4-fluorophenyl) -2-thienyl] hept-2-enoate in a manner similar to that of Example 21. NMR (CDC13, d): 1.12 (3H, t, J = 7Hz), 1.49-1.92 (4H, m), 2.18-2.30 (HH, m), 2.55-2.68 (2H, m), 9.73-2.82 (HH) ,), 2.81 (HH, d, J = 14Hz), 2.89 (HH, d, J = 14Hz), 4.01 (2H, q, J = 7Hz), 6.93-7.11 (4H, m), 7.49-7.56 (2H , m) Example 24 To a solution of ethyl 3- (4-biphenylyl) -7-chlorohept-2-enoate (0.90 g) in acetone (15 ml) was added Nal (1.55 g) at 60 ° C. After being stirred overnight, the reaction mixture was cooled, concentrated in vacuo, diluted with water, and extracted with ether. The ether extract was washed with brine, dried over MgSO4 and concentrated in vacuo. A mixture of this residue and thiourea (158 mg) in ethanol (EtOH) (15 ml) was refluxed with stirring for 24 hours. The resulting mixture was cooled and concentrated in vacuo to obtain isothiuronium salt. To a solution of potassium hydroxide (KOH) (1.74 g) in water was added this isothiuronium salt, and the mixture was refluxed with stirring for 8 hours. The reaction mixture was cooled to 0 ° C and made rapidly, by carefully adding a solution of 50% aqueous sulfuric acid (H2SO4) to acidification. The mixture was extracted with ether, and the organic layers were washed with water and brine, dried over magnesium sulfate (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluent: 5% methanol (MeOH) in chloroform (CHC13) to form 2-4-biphenylyl) -3,4,5,6-tetrahydro-2H-thiopyran -2-acetic (335 mg) as an amorphous. NMR (CDC13, d): 1.60-1.85 (4H., M), 2.30-2.39 (HH, m), 2.50-2.70 (3H, m), 2.94 (HH, d, J = 14.7Hz), 3.01 (1H , d, J = 14.7Hz), 7.34 (ÍH, dd, J = 7, 7Hz), 7.56-7.61 (4H, m), 7.68-7.71 (2H, m) MS (ESI-) m / z: 311 ( MH) Example 25 2- (4- (4-fluorophenoxy) phenyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid (200 mg) was obtained in a manner similar to that of Example 24 .

NMR (CDCI3, d): 1.60-1.84 (4H, m), 2.27-2.36 (HH, m) 2.50-2.67 (3H, m), 2.88 (HH, d, J = 15Hz), 2.97 (HH, d, J = 16Hz), 6.91 (2H, d, J = 9Hz), 6.99-7.06 (4H, m), 7.56 (2H, d, 5 J = 9Hz) MS (ESI-) m / z: 345 (MH) Example 26 2- [4- (4-Chlorophenyl) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid (310 mg) was obtained in a manner similar to that of Example 24. NMR (CDCI3, d): 1.60-1.85 (4H, m), 2.29-2.38 (HH, m), 2.52-2.69 (3H, m), 2.94 (HH, d, J = 14.7Hz), 3.01 (HH, d , J = 14.7Hz), 7.39 (2H, d, J = 8Hz), 7.50-7.54 (4H, m), 7.69 (2H, d, 15 J = 8Hz) MS (ESI-) m / z: 345 (M-H) ^^ Example 27 2- [4- (4-Bromophenyl) phenyl] -3 acid was obtained, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetic acid (120 mg) in a manner similar to that of Example 24. NMR (CDCI3, d): 1.61-1.85 (4H,) 2.29-2.36 (H) , m) 2.51-2.69 (3H, m), 2.94 (HH, d, J = 14.7Hz), 3.01 (HH, d, J = 14.7Hz), 7.45 (2H, d, J = 9Hz), 7.51 -7.57 (4H, m), 7.69 (2H, d, 5 J = 9Hz) MS (ESI-) m / z: 389 (MH) Example 28 2- [4- (4-fluorophenyl) phenyl] - 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetic acid (200 mg) in a manner similar to that of Example 24. NMR (CDC13, d): 1.60-1.85 (4H,), 2.29-2.38 ( HH, m), 2.53-2.67 (2H, m), 2.94 (HH, d, J = 15Hz), 3.01 (HH, d, J = 16Hz), 7.07-7.12 (2H,), 7.51-7.56 (4H, m), 7.69 (2H, d, J = 8.5Hz) MS (ESI-) m / z: 329 (MH) Example 29 2- [5- (4-chlorophenyl) -2-thienyl] -3 acid was obtained, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetic acid (2.5 g) in a manner similar to that of Example 24. NMR (DMS0-d6, d): 1.55-1.75 (4H,), 2.25-2.32 ( HH, m), 2.45-2.63 (3H, m), 2.14 (HH, d, J = 14Hz), 3.97 15 (HH, d, J = 14Hz), 7.02 (HH, d, J = 3.6H z), 7.40 (HH, d, J = 3.6Hz), 7.45 (2H, d, J = 8.7Hz), 7.64 (2H, d, J = 8.7Hz) MS (ESI-) m / z: 351 (MH Example 30 2- (5-Bromo-2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid (8.5 g) was obtained in a manner similar to that of Example 24.

NMR (DMSO-d6, d): 1.45-1.73 (4H, m), 2.12-2.20 (HH, m), 2.45-2.70 (4H, m), 2.87 (HH, d, J = 14.4Hz), 6.84 ( HH, d, J = 4.2Hz), 7.08 (HH, d, J = 4.2Hz) 5 Example 31 l-Ethyl-3- (3-dimethylaminopropyl) carbodimide hydrochloride (WSCD) (205 mg) was added to a mixture stirred from 1, 1-2- [4- (4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid (326 mg), (R) - (+ ) - - j methylbenzylamine (105 mg), and 1-hydroxybenzotriazole (123 mg) in dichloromethane (8 ml) under ice-cooling, and then the resulting mixture was stirred at the same temperature for 2 hours and at room temperature for 2 hours and extracted with dichloromethane. The extract was washed 15 successively with water, hydrochloric acid 0. IN, water and a saturated aqueous solution of sodium bicarbonate, dried ^^ on magnesium sulfate and evaporated in vacuo. The residue was chromatographed (eluent: toluene-ethyl acetate) on silica gel to obtain diastereomer A (160 mg) and the 20 diastereomer B (181 mg) of 2- [4- (4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-N- [1 R) -1-phenylethyl] acetamide as a colorless solid and colorless crystals, respectively. Diastereomer A: 5 Melting point: 138-160.5 ° C 27 31.0 ° (C = 0.52, MeOH) IR (KBr): 3421 (br), 1651,1288, 1244, 1124 cm "1 NMR (CDC13, d): 1.06 (3H, d, J = 6.8Hz), 1.94-2.15 (4H, m), 2.68-2.74 (2H, m), 2.99-3.26 (4H, m), 4.72-4.87 ( ÍH, m), 5.21 (ÍH, b, d, J = 8.0Hz), 6.97 (2H, d, J = 9.0Hz), 7.00-7.11 (4H, m), 7.19-7.37 (5H, m), 7.70 (2H, d, J = 9.0Hz) (+) APCl MS m / z 498 and 500 (M ++ H) Diastereomer B Melting point Í2.5-89 ° C W1: 53.4 ° (C = 0.50, MeOH) IR (KBr): 3365 (br), 1651.1288, 1246, 1122 cm "1 NMR (CDCI3, d): 1.32 (3H, d, J = 6.9Hz), 1.91 (2H, m), 2.13 (4H, m), 2.62 (2H, m), 2.99-3.30 (4H, m), 4.85 (HH, m), 5.31 (HH, br d, J = 8.0Hz), 6.74-6.80 (2H, m), 6.90-6.99 (4H, m), 7.15-7.36 (5H, m), 7.58 (2H, d, J = 9.0Hz) (+) APCl MS m / z: 498 and 500 (M ++ H) Example 32 To a solution of (2R or 2S) -2- [4- (4-chlorophenoxy) -phenyl] -3,4,5,6-tetrahydro-2H acid 1,1-dioxide. -thiopyran-2-acetic (4.75 g) obtained in Example 10, O- (2-tetrahydropyranyl) hydroxylamine (2.11 g), and 1-hydroxy-benzotriazole (1.95 g) in N, N-dimethylformamide (60 ml) were He added hydrochloride WSCD (2.77 g) After being stirred for 4 hours at room temperature, the solvent was evaporated in vacuo, and the resulting residue was dissolved in ethyl acetate (60 ml) .The solution was washed with an aqueous solution at room temperature. 5% citric acid, a solution of saturated sodium bicarbonate and brine, and dried over sulfate of magnesium The solution was concentrated under reduced pressure to form (2R or 2S) -N- (2-tetrahydropyranyloxy) -2- [4- (4-chlorophenoxy) phenyl] -3, 4, 5-dioxide , 6-tetrahydro-2H-thiopyran-2-acetamide (6.52 g) as a slightly yellow oil. NMR (CDC13, d): 1.46-2.22 (10H, m), 2.77 (HH, br), 3.02-3.28 (4H,), 3.38-3.55 (HH, m), 3.65-3.78 (HH, m), 4.37 (0.5H, s), 4.77 (0.5H, s), 6.95 (2H, d, J = 8Hz), 7.00 (2H, d, J = 8Hz), 7.29 (2H, d, J = 8Hz), 7.65 ( 2H, d, J = 8Hz), 8.28 (HH, br) MS (ESI-) m / z: 493 (MH) The following compounds were obtained in a manner similar to that of Example 32. Example 33 2- [4- (4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (140 mg) NMR (CDCl 3, d): 1.42-1.91 (10H, m), 2.23-2.36 (1H) , m), 2.49-2.72 (4H,), 2.74-2.83 (ÍH, m), 3.45-3.58 (ÍH, m), 3.71-3.83 (ÍH, m), 4.55 (ÍH, s), 4.79 ( 0.5H, s), 6.89-7.03 (4H, m), 7.27 (2H, d, J = 8Hz), 7.60 (2H, d, J = 5Hz), 7.96 (0.5H, s), 8.16 (0.5H, s) MS (ESI-) m / z: 460 (MH) EXAMPLE 34 N- (2-tetrahydropyranyloxy) -2- [4- (4-fluorophenoxy) phenyl] -3,4,5-dioxide 6-tetrahydro-2H-thiopyran-2-acetamide (307 mg) NMR (CDC13, d): 1.53-1.70 (10H, m), 2.08-2.17 (2H, m), 2.73-2.76 (2H, m), 3.02 -3.23 (4H, m) , 3.42-3.52 (HH, m), 6.98-7.05 (6H,), 7.64 (2H, d, J = 9Hz) MS (ESI-) m / z: 476 (MH) Example 35 N- (2-tetrahydropyranyloxy) -2- [4- (4-f luorof enoxi) -f-enyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (250 mg) NMR (CDCl3, d): 1.50-1.64 (6H, m), 1.74-1.78 (4H, m), 2.25-2.34 (2H , m), 2.52-2.70 (4H, m), 2.76-2.82 (HH, m), 3.49-3.51 (HH, m), 3.72-3.63 (HH, m), 6.95-7.04 (6H, m), 7.59 (2H, d, J = 9Hz) MS (ESI-) m / z: 444 (MH) Example 36 1-N- (2-tetrahydropyranyloxy) -2- [4- (4-fluorophenoxy) -phenyl] -oxide 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (152 mg) NMR (CDC13, d): 1.54-1.81 (10H, m), 2.45-2.56 (2H, m), 2.75-2.96 ( 5H,), 3.53-3 .59 (HH, m), 3.81-3.87 (HH, m), 6.95-7.04 (6H, m), 7.39 (2H, d, J = 9Hz) MS (ESI-) m / z: 460 (MH) Example 37 N- (2-tetrahydropyranyloxy) -2- [4- (4-fluorophenoxy) -phenyl] -3,4,5,6-tetrahydro-2H-thiopyran 1,1-dioxide 2-Acetamide (173 mg) NMR (CDCl 3, d): 1.45-1.75 (6H, m), 1.89-2.01 (2H, m) 2.06-2.20 (2H, m), 2.68-2.80 (2H, m), 3.00 -3.24 (4H, m), 3.40-3.55 (HH, m), 3.64-3.75 (HH, m), 4.49 (0.5H, br s), 4.75 (0.5H, br s), 6.93 (2H, d, J = 9Hz), 7.04 (2H, d, J = 9Hz ), 7.45 (2H, d, J = 9Hz), 7.67 (2H, d, J = 9Hz), 7.77 (2H, d, J = 9Hz), 7.71 (0.5H, br s), 7.90 (0.5H, br s) MS (ESI-) m / z: 536 (MH) Example 38 N- (2-tetrahydropyranyloxy) -2- [4- [4- (4-fluorophenyl) -phenoxy] phenyl] 1,1-dioxide 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (122 mg) NMR (CDCI3, d): 1.45-1.79 (6H, m), 1.88-2.02 (2H, m), 2.06-2.24 ( 2H, m), 2.66-2.62 (2H, m), 3.00-3.25 (4H, m), 3.40-3.56 (HH, m), 3.64-3.77 (HH, m), 4.41 (0.5H, br s), 4.75 (0.5H, br s), 7.00-7.18 (6H,), 7.42-7.56 (4H, m), 7.67 (2H, d, J = 9Hz), 7.75 (0.5H, br s), 7.89 (0.5H , br s) MS (ESI-) m / z: 552 (MH) Example 39 N- (2-tetrahydropyranyloxy) -2- (4-methoxyphenyl) -3, 4, 5, 6-tetrahydro 1,1-dioxide -2H-thiopyran-2-acetamide (113 mg) NMR (CDCl3, d): 1.41-1.72 (6H, m), 1.87-2.01 (2H, m), 2.06-2.21 (2H, m), 2.59-2.81 ( 2H, m), 3.00-3.25 (4H, m), 3.32-3.73 (2H, m), 3.81 (3H, s), 4.37-4.44 (0-5H, m), 4.69-4.79 (0.5H, m) , 6.91-7.03 (2H, m), 7.53-7.69 (2H, m), 7.70-7. 91 (1H, m) MS (ESI-) m / z: 396 (MH) EXAMPLE 40 N- (2-Tetrahydropyranyloxy) -2- [5- (4-f luorofenyl) -2-thienyl] -3,4 , 5, 6-tetrahydro-2H-thiopyran-2-acetamide (145 mg) NMR (CDCI3, d): 1.45-1.99 (10H, m), 2.17-2.32 (HH, m), 2.50-2.97 (3H, m), 3.40-3.51 (HH, m), 3.71-3.86 (HH, m ), 4.70 (0.5H, s), 4.86 (0.5H, s), 6.93-7.19 (4H, m), 7.52-7.67 (2H, m), 8.09 (0.5H, s), 8.22 (0.5H, s) ) MS (ESI-) m / z: 434 (MH) Example 41 N- (2-tetrahydropyranyloxy) -2- [5- (4-fluorophenyl) -2-thienyl] -3,4-dioxide, 5,6-tetrahydro-2H-thiopyran-2-acetamide (345 mg) NMR (CDC13, d): 1.39-1.79 (6H, m), 1.89-2.00 (2H, m), 2.05-2.27 (2H, m) , 2.64-2.92 (2H, m), 3.06 (HH, s), 3.09-3.16 (HH, m), 3.27-3.50 (HH, m), 3.61-3.73 (HH, m), 4.53 (0.5H, br s), 4.92 (ÍH, br s), 7.02-7.11 (2H, m), 7.16-7.27 (2H, m), 7.55 (ÍH, d, J = 8Hz), 7.57 (ÍH, d, J = 8Hz) , 7.97 (0.5H, s), 8.13 (OH, br s) Example 42 N- (2-tetrahydropyranyloxy) -2- (4-bifinyl) -3,4,5,6-tetrahydro-2H-thiopyran-2 -acetamide (330 mg) NMR (CDCl 3, d): 1.45-1.81 (10H, m), 2.29-2.38 (HH, m), 2.52-2.96 (7H, m), 3.58-3.75 (HH, m) , 7.35-7.37 (ÍH, m), 7.42-7.47 (2H, m), 7.56-7.64 (4H, m), 7.71-7.75 (2H, m) MS (ESI-) m / z: 410 (MH) Example 43 N- (2-tetrahydropyranyloxy) -2- (4-1,1-dioxide -biphenylyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (390 mg) NMR (CDCl 3, d): 1.38-1.66 (6H, m), 1.95-2.03 (2H, m), 2.12-2.21 (2H, m), 2.73-2.84 (2H, m), 2.89 (HH, s), 2.96 (HH, s), 3.04-3.31 (4H, nt), 3.50-3.62 (HH, m), 7.35-7.47 (3H, m), 7.58-7.60 (2H, m), 7.65-7.70 (2H, m), 7.77-7.81 (2H, m) MS (ESI-) m / z: 442 (MH) Example 44 1, 1-N- (2-tetrahydropyranyloxy) -2- [4- (4-chloro-phenyl) -phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (300 mg) NMR (CDCI3, d): 1.60-1.66 (6H, m), 1.94-2.03 (2H, m), 2.13-2.21 (2H, m), 2.76-2.84 (2H, m), 2.89-2.96 (2H, m) , 3.07-3.27 (4H, m), 3.53-3.65 (HH, m), 7.41 (2H, d, J = 8.5Hz), 7.51 (2H, d, J = 8.5Hz), 7.60-7.64 (2H, m ), 7.76-7.80 (2H, m) MS (ESI-) m / z: 476 (MH) Example 45 N- (2-tetrahydropyranyloxy) -2- [4- (4-bromophenyl) phenyl 1,1-dioxide ] -3, 4, 5, 6-tet Rahydro-2H-thiopyran-2-acetamide (100 mg). NMR (CDCI3, d): 1.44-1.62 (10H, m), 2.10-2.20 (2H, m), 2.76-2.84 (2H, m), 3.05-3.31 (4H, m), 3.53-3.65 (H, m) ), 7.45 (2H, d, J = 9Hz), 7.56-7.64 (4H, m), 7.70-7.77 (2H, m) MS (ESI-) m / z: 520 (MH) Example 46 1,1-dioxide of N- (2-tetrahydropyranyloxy) -2- [4- (4-fluorophenyl) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (230 mg) NMR (CDC13, d): 1.45-1.70 (10H, m), 2.12-2.19 (2H, m) 2.79-2.81 (2H, m), 3.05-3.32 (4H, m), 3.55-3.64 (HI, m), 7.13 (2H, dd, 3 = 9, 9Hz), 7.52-7.61 (4H, m), 7.73-7.78 (2H, m) MS (ESI-) m / z: 460 (MH) Example 47 N- (2-) 1,1-dioxide tetrahydropyranyloxy) -2- (4-phenoxybenzyl) -3,4,5,6,6-tetrahydro-2H-thiopyran-2-carboxamide (360 mg) NMR (CDCl 3, d): 1.45-2.31 (12H, m), 2.42-2.63 (HH, m), 3.03-3.20 (3H, m), 3.43 (HH, d, J = 14Hz), 3.57 -3.70 (HH, m), 3.84-4.02 (HH, m), 4.91, 5.11 (HH, s), 6.91 (2H, d, J = 8Hz), 6.97-7.14 (3H, m), 7.19 (2H, t, J = 8Hz), 7.28-7.48 (2H, m), 9.99, 10.07 (HH, s) MS (ESI-) m / z: 458 (MH) Example 48 N- (2-tetrahydropyranyloxy) -2- ( 4- phenoxybenzyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-carboxamide (320 mg) NMR (CDC13, d): 1.33-2.00 (12H, m), 2.47-2.59 (1H, m), 2.64-2.90 (3H, m), 3.08-3.22 (ÍH, m), 3.50-3.65 (ÍH, m), 3.75-4.00 (ÍH, m), 4.70, 4.98 (ÍH, s), 6.87- 7.20 (7H, m), 7.32 (2H, t, J = 8Hz), 9.70 (1H, s) MS (ESI-) m / z: 426 (MH) Example 49 N- (2-1,1-dioxide) tetrahydropyranyloxy) -2- (4-biphenylylmethyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-carboxamide (152 mg) NMR (CDCl 3, d): 1.54-2.35 (12H, m), 2.45- 2.66 (ÍH, m), 3.08-3.25 (3H, m), 3.33-3.55 (ÍH, m), 3.56-3.70 (ÍH, m), 3.82-4.08 (ÍH, m), 4.95, 5.14 (ÍH, s ), 7.23-7.36 (3H, m), 7.42 (2H, t, J = 8Hz), 7.47-7.67 (4H, m), 10.01- 10.08 (1H, s) MS (ESI-) m / z: 442 (MH) Example 50 N- (2 -tetrahydropyranyloxy) -2- (4-phenoxypienyl) -1,3-dithian-2-acetamide (150 mg) NMR (DMSO-ds, d): 1.47-1.62 (6H, m), 1.85-1.90 (2H, m ), 2.73 (2H, s), 2.89 (4H, br), 3.33 (2H, m), 4.57 (ÍH, s), 6.98 (2H, d, J = 8.0Hz), 7.03 (2H, d, J = 8.0Hz), 7.16 (HI, dd, J = 8.0, 8.0Hz), 7.40 (2H, dd, J = 8.0, 8.0 Hz), 7.83 (2H, d, J = 9.0Hz) MS (ESI-) m / z: 444.1 (MH) Example 51 N- (2-tetrahydropyranyloxy) -2- [5- (4-N-1,1-dioxide -chlorophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (250 mg) NMR (CDC13, d): 1.45-1.67 (10H, m), 1.90-1.97 ( 2H, m), 2.67-3.12 (6H, m), 3.621-3.68 (HH, m), 7.24-7.26 (2H, m), 7.35 (2H, d, J = 8.7H7), 7.52 (2H, d, J = 8.7 Hz) MS (ESI-) m / z: 482 (MH) Example 52 N- (2-tetrahydropyranyloxy) -2- (5-bromo-2-thienyl) -3 1,1-dioxide, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (190 mg) NMR (CDCl 3, d): 1.50-2.17 (11H, m), 2.65-3.10 (6H, m), 3.47-3.58 (HH, m), 3.72-3.81 (HH, m), 7.00-7.05. (2H, m) MS (ESI-) m / z: 450 (MH) Example 53 1, 1-dioxide (2R or 2S) -N- (2-tetrahydropyranyloxy) -2- (5-bromo-2-thienyl) ) -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (80 mg) from 1,1-dioxide acid (2R or 2S) 2- (5-bromo-2-thienyl) - 3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid (63 mg) obtained in Example 13. NMR (CDC13, d): 1.50-2.17 (11H, m), 2.65-3.10 (6H, m ), 3.47-3.58 (HH,), 3.72-3.81 (HH, m), 7.00-7.05 (2H, m) 5 MS (ESI-) m / z: 450 (MH) Example 54 To a mixture of 1.1 - (2R or 2S) -N- (2-tetrahydropyranyloxy) -2- [4- (4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide dioxide (6.51 g) ) obtained in ls Example 32 in methanol (40 ml) was added 10% hydrogen chloride in methanol (10 ml) at room temperature. After being stirred for 30 minutes, the solution was concentrated. The residue was purified by column chromatography on silica gel (eluent: hexane-EtOAc 1: 1) to form 1,1-dioxide of (2R or 2S) - (-) - N -hydroxy-2- [4- (4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-^^ acetamide (optical isomer A, 4.72 g) as a white crystalline. 20 w ": -13.7 ° C (C = 0.98, MeOH) Anal Chiral HPLC: column: Chiralpak AS (4.6 x 250 mm, Daicel Chemical Industries, Ltd.) eluent: n-hexane-ethanol-TFA (700: 300 : 1) 5 circulation speed: 1.0 ml / minute detection: 220 nm retention time: 18.2 minutes The following compounds were obtained in a manner similar to that of Example 54. Example 55 N-hydroxy-2- [4- (4 -chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (61 mg) NMR (DMSO-d6, d): 1.32-1.78 (4H, m), 2.30-2.58 (4H ,), 2.60-2.73 (2H, m), 6.96-7.08 (4H, m), 7.43 (2H, d, J = 8Hz), 7.55 (2H, d, J = 8Hz), 10.19 (H, s) MS (ESI-) m / z: 376 (MH) EXAMPLE 56 N-Hydroxy-2- [4- (4-fluorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran 1,1-dioxide -2-Acetamide (220 mg) NMR (DMSO-d6, d): 1.75-2.03 (4H, m), 2.99 (HH, d, J = 14Hz), 3.19 (HH, d, J = 14Hz), 3.34-3.50 (4H, m), 6.94 (2H, d, J = 9Hz), 7.09-7.14 (2H, m), 7.23-7.29 (2H,), 7.53 (2H, d, J = 9Hz), 8.74 (IH, s) MS (ESI- ) m / z: 392 (MH) EXAMPLE 57 N-Hydroxy-2- [4- (4-fluorofinoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (143 mg) NMR ( DMSO-ds, d): 1.46-1.73 (4H,), 2.35-2.49 (4H, m), 2.64-2.71 (2H, m), 6.93 (2H, d, J = 9Hz), 7.05-7.09 (2H, m), 7.20-7.26 (2H, m), 7.53 (2H, d, J = 9Hz), 8.62 (IH, s), 10.18 (IH, s) MS (ESI-) m / z: 360 (MH) Example 58 1-N-hydroxy-2- [4- (4-fluorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (80 mg) NMR (DMSO-d6, d) ): 1.47-1.65 (4H, m), 1.95-2.02 (HH, m), 2.25-2.44 (3H,), 2.57 (HH, d, J = 14Hz), 2.70 (1H, d, J = 14Hz), 6.96 (4H, d, J = 9Hz), 7.07-7.12 (2H, m), 7.22-7.28 (2H, m), 7.40 (2H, d, J = 9Hz), 8.64 (H, s), 10.31 (H) , s) MS (ESI-) m / z: 376 (MH) Example 59 1,1-dioxide of N-hydroxy-2- [4- (4-br omophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (104 mg) NMR (CDC13, d): 1.86-1.97 (2H, m), 2.02-2.23 (2H, 2.60-2.80 (2H, m), 3.01-3.24 (4H, m), 6.93 (2H, d, J = 9Hz) , 7.01 (2H, d, J = 9Hz), 7.46 (2H, d, J = 9Hz), 7.64 (2H, d, J = 9Hz) MS (ESI-) m / z: 452 (MH) Example 60 1, 1-Dioxide of N-hydroxy-2- (4- [- [(4-fluorophenyl) phenoxy] phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (63 mg) NMR (CDC13 , d): 1.87-2.00 (2H, m), 2.04-2.25 (2H, m), 2.60-2.82 (2H, m), 3.01-3.25 (4H, m), 7.00-7.19 (6H, m), 7.47 -7.57 (4H, m), 7.64 (2H, d, J = 9Hz) MS (ESI-) m / z: 468 (MH) Example 61 1, 1-N-hydroxy-2- (4-methoxyphenyl) dioxide -3, 4,5,6-tetrahydro-2H-thiopyran-2-acetamide (21 mg) NMR (DMS0-d6, d): 1.70-2.05 (4H, m), 2.39-2.52 (H, m), 2.81 -2.91 (ÍH, m), 2.95-3.22 (4H, m), 3.26 (3H, s), 6.91 (2H, d, J = 9Hz), 7.45 (2H, d, J = 9Hz), 8.70 (ÍH, s), 10.46 (HH, s) MS (ESI-) m / z: 312 (MH) Example 62 N-hydroxy-2- [5- (4-fluorophenyl) -2-thienyl) -34,5,6-tetrahydro-2H-thiopyran-2-acetamide (87 mg) NMR (CDCl 3, d): 1.45-1.85 (4H, m), 2.35-2.74 (4H, m), 2.46 (1H, d) , J = 14Hz), 2.66 (HH, d, J = 14Hz), 7.17-7.33 (3H, m), 7.45 (HH, d, J = 3Hz), 7.64-7.77 (2H, m), 8.74 (H, s) MS (ESI-) m / z: 350 (MH) Example 63 N-hydroxy-2- [5- (4-fluorophenyl) -2-thienyl 1,1-dioxide] -3, 4, 5, 6 -tetrahydro-2H-thiopyran-2-acetamide (286 mg) NMR (CDC13, d): 1.69-2.07 (4H, m), 2.35-2.48 (2H, m), 2.94-3.54 (4H, m), 7.17- 7.33 (3H, m), 7.45 (HH, d, J = 3Hz), 7.64-7.77 (2H, m), 8.74 (HH, s) MS (ESI-) m / z: 382 (MH) Example 64 N- hydroxy-2- (4-biphenylyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (230 mg) NMR (DMS0-d6, d): 1.61-1.79 (4H, m), 2.39 -2.56 (2H, m), 2.65-2.75 (3H, m), 2.89 (ÍH, s), 7.36 (ÍH, dd, 3 = 1, 7Hz), 7.47 (2H, dd, J = 7, 7Hz), 7.64-7.69 (6H, m), 8.63 (OH, s) MS (ESI-) m / z: 326 (MH) EXAMPLE 65 N-Hydroxy-2- (4-biphenylyl) -3,1-dioxide, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (230 mg) NMR (DMSO-ds , d): 1.77-2.05 (4H, m), 2.49-2.51 (2H, m), 3.19-3.41 (4H, m), 7.41 (HI, dd, J = 7.5, 7.5Hz), 7.49 (2H, dd , J = 7.5, 7.5Hz), 7.65-7.71 (6H, m), 8.74 (OH, s) MS (ESI-) m / z: 358 (MH) Example 66 1, 1-N-hydroxy-2-dioxide - [4- (4-chlorophenyl) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (150 mg) NMR (DMSO-d5, d): 1.78-2.04 (4H, m) , 2.91-3.10 (2H, m), 3.17-3.36 (4H, m), 7.54 (2H, d, J = 9Hz), 7.61-7.69 (4H, m), 7.73 (2H, d, J = 9Hz ), 8.72 (OH, s) Example 67 1, 1-N-hydroxy-2- [4- (4-bromophenyl) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide dioxide (70 mg) NMR (DMSO-dg, 6): 1.77-2.06 (4H, m), 2.93-3.08 (2H, m), 3.19-3.36 (4H, m), 7.61-7.70 (8H, m), 8.74. (HH, s) MS (ESI-) m / z: 436 (MH) Example 68 N-hydroxy-2- [4- (4-fluorophenyl) phenyl] 1,1-dioxide] -3, 4, 5, 6 -tetrahydro-2H-thiopyran-2-acetamide (160 mg) NMR (DMSO-ds, d): 1.77-2.05 (4H, m), 2.93-3.54 (6H, m), 7.31 (2H, dd, 3 = 9 , 9Hz), 7.63-7.77 (6H, m), 8.73 (H, s), 10.53 (H, s) MS (ESI-) m / z: 376 (MH) EXAMPLE 69 1,1-N-Hydroxy-2- (4-phenoxybenzyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-carboxamide dioxide ( 199 mg) NMR (CDC13, d): 1.47-2.20 (5H, m), 2.49-2.62 (HH, m), 2.96-3.20 (3H, m), 3.43 (HH, d, J = 14Hz), 6.89 ( 2H d, J = 8Hz), 6.98 (2H, d, J = 8Hz), 7.05-7.18 (3H, m) 7.33 (2H, d, J = 8Hz), 7.96 (IH, br s), 9.98 (IH, bs) MS (ESI-) m / z: 374 (MH) EXAMPLE 70 N-Hydroxy-2- (4-phenoxybenzyl) -3,4,5,6-tetrahydro-2H-5 thiopyran-2-carboxamide (203 mg ) Melting point: 124-126 ° C NMR (CDC13, d): 1.22-1.38 (HH, m), 1.45-1.66 (2H, m), 1.70-1.83 (HH, m), 1.88-1.98 (HH, ), 2.43-2.55 (ÍH, m), 2.60-2.75 (2H, m), \ W 2.80 (HH, d, J = 14Hz), 3.15 (HH, d, J = 14Hz), 6.90 (2H, d, J = 8Hz), 7.00 (2H, d, J = 8Hz), 7.05-7.15 ( 3H, m), 7.33 (2H, t, J = 8Hz), 9.47 (OH, s) MS (ESI-) m / z: 342 (MH) 15 Example 71 N-hydroxy-2- 1,1-dioxide (4-biphenylylmethyl) - ^^ 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-carboxamide (78 mg) Melting point: 101-104 ° C NMR (DMSO-d6, d): 1.58-2.18 (6H, m), 3.06-3.17 20 (HH, m), 3.39 (HH, d, J = 14Hz), 3.49-3.64 (HH, m), 3.65 (HH, d, J = 14Hz), 7 , 31 (2H, d, J = 8Hz), 7.37 (ÍH, d, J = 8Hz), 7.46 (2H, t, J = 8Hz), 7.59 (2H, d, J = 8Hz), 7.65 (2H, d , J = 9Hz), 9.20 (HH, s) 5 MS (ESI-) m / z: 358 (MH) Example 72 N-hydroxy-2- (4-phenoxyphenyl) -1, 3-dithian-2-acetamide ( 88 mg) NMR (DMS0-d6, d): 2.27-2.38 (2H, m), 3.43. (2H, s), 3.60-3.67 (2H, m), 3.90-3.86 (2H, m), 7.00 (2H, d, J = 9.0Hz), 7.10 (2H, d, J = 8.0Hz), 7.22 ( ÍH, dd, J = 8.0, 8.0Hz), 7.45 (2H, dd, J = 8.0, 8.0Hz), 8.04 (2H, d, J = 8.0Hz), 8.94 (IH, s) MS (ESI) m / z: 360.1 (MH) Example 73 N-hydroxy-2- [5- (4-chlorophenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-1,1-dioxide Acetamide (200 mg) NMR (DMS0-d6, d): 1.74-2.02 (4H, m), 2.96-3.52 (6H, m), 7.22 (HI, d, J = 3.6Hz), 7.47-7.53 (3H, m), 7.67 ( 2H, d, J = 6.7Hz), 8.85 (OH, s), 10.59 (OH, s) MS (ESI-) m / z: 398 (MH) Example 74 1,1-dioxide N-hydroxy-2 - (5-Bromo-2-thienyl) - 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (140 mg) NMR (DMS0-d6, d): 1.73-2.00 (4H, m), 2.26-2.33 (ÍH, m), 2.86-2.96 (2H, m), 3.11-3.23 (2H, m), 3.40-3.45 (ÍH, m), 7.03 (ÍH, d, J = 3.9Hz), 7.22 ( HH, d, J = 3.9Hz), 8.86 (HH, s), 10.57 (HH, s) MS (ESI-) m / z: 366 (MH) Example 75 1,1-dioxide (2R or 2S) - N-hydroxy-2- (5-bromo-2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (65 mg) from 1,1-dioxide (2R or 2S) ) -N- (2-tetrahydropyranyloxy) -2- (5-bromo-2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (80 mg) obtained in Example 53 w ": -17.1 ° C (C = 0.435, DMF) NMR (DMSO-d6, d): 1.73-2.00 (4H,), 2.26-2.33 (HI, m), 2.96-2.96 (2H,), 3.11- 3.23 (2H, m), 3.40-3.45 (HH, m), 7.03 (HH, d, J = 3.9Hz), 7.22 (HH, d, J = 3.9Hz), 8.86 (HH, s), 10.57 (HH) , s) MS (ESI-) m / z: 366 (MH) Optical purity: 95% ee Chiral anal HPLC: column: Chiralpak AS (4.6 x 250 mm, Daicel Chemical Industries, Ltd.) eluent: n-hexane- Ethanol-TFA (700: 300: 1) circulation speed: 1.0 ml / minute detection: 220 nm The following compounds were obtained in a manner similar to that of preparation 1-4) Example 76 1,1-acid dioxide 2- [4- (4-fluorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid (450 mg) 5 NMR (CDC13, d): 1.87-2.21 (4H, m) , 2.67-2.85 (2H, m), 3.03-3.15 (2H, m), 3.21 (HH, d, J = 16Hz), 3.62 (HH, d, J = 16Hz), 6.94-7.04 (6H, m), 7.59 (2H, d, J = 9Hz) MS (ESI-) m / z: 377 (MH) is Example 77 2- [4- (4-bromophenoxy) phenyl] -3,4-acid dioxide, 5,6-tetrahydro-2H-thiopyran-2- NMR acetic acid (CDCl3, d): 1.75-2.02 (4H, m), 2.08-2.21 (2H, m), 2.63-2.85 (2H, m), 3.02-3.16 (2H, 15 m), 3.21 (HH, d, J = 16Hz), 3.60 (HH, d, J = 16Hz), 6.92 (2H, d, J = 9Hz), 7.00 (2H, d, ^ J = 9Hz), 7.46 (2H, d, J = 9Hz), 7.60 (2H, d, J = 9Hz) MS (ESI-) m / z: 439 (MH) 20 Example 78 2- (4-methoxyphenyl) -3, 4, 5 acid , 6-tetrahydro-2H-thiopyran-2-acetic NMR (CDCI3, d): 1.71-2.00 (4H, m), 2.07-2.20 (2H, m), 2.60-2.86 (2H, m), 2.99-3.14 ( 2H, 5), 3.19 (HH, d, J = 15.5Hz), 3.60 (HH, d, J = 15.5Hz), 3.81 (3H, s), 6.82 (2H, d, J = 9Hz), 7.56 (2H , d, J = 9Hz) MS (ESI-) m / z: 297 (MH) Example 79 2- [5- (4-Fluorophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H acid -thiopyran-2-acetic NMR (CDC13, d): 1.70-2.02 (2H, m), 2.09-2.24 (2H, m), 2.67-2.86 (2H, m), 3.02-3.20 (2H, m), 3.19 (HH, d, J = 15Hz), 3.46 (HH, d, J = 15Hz), 7.06 (2H, dd, J = 8Hz, 8Hz), 7.15 (HH, d, J = 3Hz), 7.21 (HH, d , J = 3Hz), 7.46- 7.62 (2H, m) MS (ESI-) m / z: 367 (MH) Example 80 2- (4-biphenylyl) -3, 4, 5, 1,1-dioxide, 6-tetrahydro-2H-t? Opyran-2-acetic (0.33 g) NMR (CDCI3, d): 1.80-2.01 (2H, m), 2.11-2 .19 (2H, m), 2.69-2.76 (ÍH, m), 2.82-2.92 (ÍH, m 3.02-3.16: 2H, m 3.24 HH, d, J = 15.6Hz), 3.67 (HH, d, J = 15.6Hz), 7.37-7.46 (2H, m), 7.58-7.63 (4H, m), 7.71 (2H, d, J = 9Hz) MS (ESI-) m / z: 343 (MH) EXAMPLE 81 2- [4- (4-Chlorophenyl) phenyl] 1,1-dioxide] -3, 4, 5 , 6-tetrahydro-2H-thiopyran-2-acetic acid (275 mg) NMR (CDC13, d): 1.79-2.00 (2H,), 2.10-2.19 (2H, m), 2.66-2.89 (2H, m), 3.02 -3.24 (2H, m), 3.23 (HH, d, J = 16Hz), 3.65 (HH, d, J = 16Hz), 7.40 (2H, d, J = 9Hz), 7.50 (2H, d, J = 8.5 Hz), 7.5-7 (2H, d, J = 8.5Hz), 7.70 (2H, d, J = 9Hz) MS (ESI-) m / z: 377 (MH) Example 82 1,1-2-acid dioxide - [4- (4-bromophenyl) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid (105 mg) NMR (CDCl 3, d): 1.70-2.20 (4H, m), 2.72. -2.92 (2H, m), 3.05-3.16 (2H, m), 3.25 (HH, d, J = 16Hz), 3.67 (HH, d, J = 16Hz), 7.44 (2H, d, J = 9Hz ), 7.55-7.58 (4H, m), 7.71 (2H, d, J = 9Hz) MS (ESI-) m / z: 421 (MH) EXAMPLE 83 1,1-Dioxide of 2- [4- (4 -fluorophenyl) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid (220 mg) NMR (CDCI3, d): 1.80-2.18 (4H, m), 2.69-2.91 (HH, m), 3.04-3.16 (3H, m), 3.24 (HH, d, J = 16Hz), 3.66 (HH, d, J = 16Hz), 7.12 (2H, dd, 3 = 9, 9Hz), 7.52-7.59 (4H,), 7.70 (2H, d, J = 8.5Hz) MS (ESI-) m / z: 361 (MH) Example 84 A mixture of 2- [4- (4-chlorophenoxy) phenyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid (56 g), potassium permanganate (48.8 g) and benzyltrimethylchloride Ammonium (2.97 g) in water-methylene chloride (2: 1, 1.5 1) was stirred for 3 hours at room temperature. Then, the reaction mixture was poured into a saturated solution of sodium sulfite (500 ml), the solution was acidified with 4N hydrochloric acid. The organic layer was separated and the aqueous layer was extracted with chloroform (400 ml x 2). The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel (eluent: chloroform-methanol 10: 1) to form 2- [4- (4-chlorophenoxy) phenyl] -3, 4, 5-dioxide. , 6-tetrahydro-2H-thiopyran-2-acetic acid (17.2 g) as a colorless crystal. Melting point: 191-193 ° C Example 85 N-hydroxy-2- (4-phenoxyphenyl) -1,3-dithiane-2-acetamide 1,1,3,3-tetraoxide (56 mg) was obtained in a manner similar to that of preparation 1-4). NMR (DMSO-d6, d): 2.27-2.38 (2H, m), 3.43 (2H, s) 3.60-3.67 (2H, m), 3.80-3.88 (2H, m), 7.00 (2H, d, J = 8.0Hz), 7.10 (2H, d, J = 8.0Hz), 7.22 (ÍH, dd, J = 8.0, 8.0Hz), 7.45 (2H, dd, J = 8.0, 8.0Hz), 8.04 (2H, d, J = 8.0Hz), 8.94 (H, s) MS (ESI-) m / z: 424-1 (MH) Example 86 To a solution of 2- [4- (4-fluorophenoxy-phenyl] -3,4 acid 5,6-tetrahydro-2H-thiopyran-2-acetic acid (300 mg) in MeOH was added dropwise titanium (III) chloride (2.67 ml) (a solution in hydrochloric acid 10% by weight) in MeOH and hydrogen peroxide. hydrogen (0.69 ml) (30% aqueous solution) at room temperature, after being stirred for 15 minutes, the reaction was stopped by adding water. The reaction mixture was extracted with EtOAc and the solution was washed with brine, dried over MgSO and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluent: 5% MeOH in CHC13) to form 2- [4- (4-fluorophenoxy) phenyl] -3, 4, 5, 6- tetrahydro-2H-thiopyran-2-acetic acid (150 mg) as an amorphous. NMR (CDC13, d): 1.55-1.76 (4H, m), 2.45-2.62 (4H, m), 3.05-3.07 (2H, m), 6.95-7.07 (6H, m), 7.39 (2H, d, J = 9Hz) MS (ESI-) m / z: 361 (MH) EXAMPLE 87 2- [5- (4-Chlorophenyl) -2-thienyl] 1,1-dioxide was obtained] -3, 4, 5, 6 -tetrahydro-2H-thiopyran-2-acetic acid (1.95 g) in a manner similar to that of preparation 1-4). NMR (DMSO-ds, d): 1.76-1.90 (4H, m), 3.16-3.55 (6H, m), 7.19 (ÍH, d, J = 3.6Hz), 7.47-7.52 (3H, m), 7.68 ( 2H, d, J = 9.4Hz) Example 88: 2- (5-Bromo-2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid 1,1-dioxide ( 6.0 g) in a manner similar to that of preparation 1-4). NMR (DMSO-ds, d): 1.74-1.87 (4H, m), 2.30-2.37 (HH, m), 3.07-3.56 (5H, m), 7.02 (HH, d, J = 4.2Hz), 7.21 ( ÍH, d, J = 4.2Hz) MS (ESI-) m / z: 351 (MH) Example 89 A mixture of 2- [4- (4-bromophenoxy) phenyl] -3, 1,1-dioxide,, 5,6-tetrahydro-2H-thiopyran-2-acetic acid (130 mg), 4-fluorobenzeneboronic acid (49.7 mg) and tetrakis (triphenylphosphine) palladium (0) (3.4 mg) in a mixture of 1, 2-dimethoxyethane (0.3 ml) and 2M aqueous sodium carbonate (0.5 ml) was refluxed for 6 hours. The mixture was acidified with 4N hydrochloric acid to pH 3 and extracted with ethyl acetate. The separated organic phase was washed with brine, dried over sodium sulfate and evaporated in vacuo to form 2- [4- [4- (4-fluorophenyl) phenoxy) phenyl] -3, 4-acid dioxide. , 5,6-tetrahydro-2H-thiopyran-2-acetic acid (116 mg) as an oil. NMR (CDCI3, d): 1.75-2.02 (4H, m), 2.08-2.21 (2H,), 2.64-2.84 (2H,), 3.01-3.17 (2H, m), 3.23 (ÍH, d, J = 15Hz ), 3.62 (ÍH, d, 7.15Hz), 7.04 (2H, d, J = 9Hz), 7.07-7.16 (4H, m), 7.41-7.56 (4H, m), 7.61 (2H, d, J = 9Hz ) MS (ESI-) m / z: 453 (MH) Example 90 n-Butyl lithium 1.6M in hexane (1.63 ml) was added dropwise to a solution of diisopropylamine (261 mg) in THF (10 ml) under cooling in ice bath and a nitrogen atmosphere. After being stirred under the same conduction for 30 minutes, a solution of methyl 1,4,4-tetrahydro-2H-thiopyran-2-carboxylate 1,1-dioxide (450 mg) in THF (8 mg) was added. ml) and the mixture was stirred for 45 minutes under cooling with dry ice-acetone. A solution of 4-phenoxybenzyl bromide (719 mg) in THF (8 ml) was added to this mixture under the same condition. Then, the mixture was stirred for 2 hours at the same temperature for 2 hours under cooling in an ice bath and 2 hours at room temperature, a saturated aqueous solution of ammonium chloride was added to the reaction mixture. The resulting mixture was extracted with AcOEt. The extract was washed with 5% hydrochloric acid, an IVM sodium bicarbonate solution and brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (SiO2) (eluent: hexane-AcOEt, 6: 1) to form 2- (4-phenoxybenzyl) 3,4,5,6-tetrahydro-1,1-dioxide -2H-thiopyran-2-carboxylic acid methyl ester (745 mg) as an oil. NMR (CDC13, d): 1.68-1.92 (2H, m), 2.02-2.34 (4H, m), 3.10-3.30 (2H, m), 3.17 (H, d, J = 14Hz), 3.74 (H, d) , J = 14Hz), 3.83 (3H, s), 6.91 (2H, d, J = 8Hz), 7.00 (2H, d, J = 8Hz), 7.06-7.18 (3H, m), 7.34 (2H, t, J = 8Hz) Example 91 Methyl 2- (4-phenoxybenzyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-carboxylate (605 mg) was obtained in a manner similar to that of Example 90. NMR (CDCI3, d): 1.46-1.82 (4H, m), 1.86-1.96 (HH, m) 2.28-2.40 (HH, m), 2.52-2.62 (HH, m), 2.69-2.80 (HH, m), 3.07 (2H, s), 3.71 (3H, s), 6.99 (2H, d, J = 8Hz), 7.00 (2H, d, J = 8Hz), 7.06-7.14 (3H, m), 7.33 (2H, t , J = 8Hz) Example 92 1 was obtained, Methyl 2- (4-biphenylylmethyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-carboxylate (250 mg) 1-dioxide in a manner similar to that of preparation 90. NMR (CDCl 3 , d): 1.72-1.93 (2H, m), 2.06-2.20 (3H, m), 2.25-2.37 (HH, m), 3.12-3.30 (2H, m), 3.24 (HH, d, J = 14Hz) , 3.81 (HH, d, J = 14Hz), 3.86 (3H, s), 7.23 (2H, d, J = 8Hz), 7.30-7.38 (HH, m), 7.43 (2H, t, J = 8Hz), 7.49-7.58 (4H, m) Example 93 To a stirred solution of ethyl 3-hydroxy-3- (methoxyphenyl) -7-mercaptoheptanoate (3.00 g) in dichloromethane (20 ml) was added trifluoroacetic acid (1 ml) at room temperature. environment under nitrogen. After one hour, the mixture was cooled rapidly by adding triethylamine (1 ml) with ice cooling and concentrated in vacuo. The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The separated organic phase was washed with brine, dried over sodium sulfate and evaporated in vacuo. The oil obtained was purified by column chromatography on silica gel (eluted with 5-10% ethyl acetate in n-hexane) to form 2- (4-methoxyphenyl) -3,4,5,6-tetrahydro-2H Ethyl-2-ethyl acetate (2.216 g) as an oil. NMR (CDC13, d): 1.05 (3H, t, J = 7Hz), 1.50-1.84 (5H, m), 2.25-2.36 (HH, m), 2.45-2.71 (2H, m), 2.79 (HH, d) , J = 14Hz), 2.91 (ÍH, d, J = 14Hz), 3.81 (3H, s), 3.93 (2H, q, J = 7Hz), 6.88 (2H, d, J = 9Hz), 7.55 (2H, d, J = 9Hz) Example 94 To a mixture of ethyl 3-oxo-3- (4-phenoxyphenyl) -propanoate (500 mg) and 1,3-propanedithiol (2 ml) was added boron trifluoride diethyl etherate ( 2 ml) at 0 ° C. After being stirred at room temperature for 3 hours, the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (50 g) (eluent: ethyl acetate: hexane (1:10)) to form 2- (4-phenoxyphenyl) -1,3-dithian-2-acetate. of ethyl (370 mg) as a yellow oil. NMR (CDC13, d): 1.12 (3H, t, J = 7.0Hz), 1.94-2.01 (2H, m), 2.75-2.81 (4H, m), 3.13 (2H, s), 4.00 (2H, q, J = 7.0Hz), 6.98 (2H, d, J = 8.5Hz), 7.03 (2H, d, J = 7.0Hz), 7.12 (IH, dd, J, = 7.0, 7.0Hz), 7.34 (2H, dd , J = 7.0, 7.0Hz), 7.88 (2H, d, J = 8.5Hz) - MS (ESI-) m / z: 374 (MH) Example 95 A mixture of 2- (5-bromo-2-thienyl) 3, 4, 5,6-tetrahydro-2H-thiopyran-2-t-butyl acetate (199 g) and 90% aqueous trifluoroacetic acid (1.0 1) was stirred for 2 hours at room temperature. The mixture was diluted with water (1.5 1) and stirred for 1 hour with ice cooling, the separated solid was collected and washed with water (500 ml) to form 2- (5-bromo-2-thienyl) - 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetic (166.2 g). NMR (DMS0-d6, d): 1.45-1.73 (4H, m), 2.12-2.20 (HH, m), 2.45-2.70 (5H, m), 2.87 (HH, d, J = 14.4Hz), 6.84 ( HH, d, J = 4.2Hz), 7.08 (HH, d, J = 4.2Hz) MS (ESI-): 319 (MH) Example 96 To a solution of 1,1-dioxide (2S) -N- ( 2-tetrahydropyrazyloxy) -2- [5- (3- (2- (tert-butyl) (diphenyl) silyloxy) ethylaminocarbonyl-amino) phenyl) -2-thienyl] -3, 4,5,6-tetrahydro-2H- thiopyran-2-acetamide (500 mg) in tetrahydrofuran (3 ml) was added a solution of tetrabutylammonium fluoride IM in tetrahydrofuran (1.0 ml) at 0 ° C and the reaction mixture was stirred at room temperature for 3 hours. The resulting mixture was extracted with ethyl acetate. The organic layer was washed with water, an aqueous solution of 10% citric acid, saturated aqueous sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel 60 (eluent: 6% methanol chloroform) to form 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- ((2-hydroxyethyl) -aminocarbonylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (70 mg) as a white amorphous. NMR (CDC13, d): 1.46 (2H, br), 1.52-1.68 (4H, m), 1.94 (2H, br), 2.04-2.24 (2H, m), 2.67- 2.88 (2H, m), 3.00-3.06 (2H, m), 3.11 (2H, m), 3.30-3.47 (2H, m) , 3.72 (2H, td, J = 7.0, 7.0Hz), 4.24 (2H, td, J = 7.0, 7.0Hz), 4.52 (1 / 2H, br), 4.82 (1 / 2H, br), 6.80 (HI) , s), 7.18-7.46 (6H, m), 7.60 (ÍH, s), 8.32 (1 / 2H, s), 8.46 (1 / 2H, s) MS (ESI-): 550.5 (MH) Example 97 Auna solution of 2- (5-bromo-2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetic acid 1,1-dioxide in a mixture of acetonitrile (560 ml) ) and ethanol (800 ml) was added a solution of R- (+) -a-methylbenzylamine (28.8 g) in ethanol (40 ml) at 50 ° C. After allowing to cool to room temperature for 2 hours, the mixture was stirred for 2 hours at room temperature and 2 hours with cooling with ice in additional form. The separated solid was collected and washed with acetonitrile (140 ml) to form (2S) -2- (5-bromo-2-thienyl) -3,4,5,6-tetrahydro-2H- 1,1-dioxide. thiopyran-2-N- [(R) -1-phenylethyl] acetamide (66.2 g). The absolute configuration was determined by X-ray crystallographic analysis. NMR (DMSO-d6, d): 1.35 (3H, d, J = 6.6Hz), 1.60- 1.04 (4H,), 2.18-2.32 (ÍH, m), 2.86-3.10 (3H, m), 3.24 (HH, d, J = 15.6Hz), 3.36-3.52 (2H, m), 4.15 (HH, q, J = 6.6Hz), 6.96 (HH, d, J = 4.2Hz), 7.14 (ÍH, d, J = 4.2Hz), 7.24-7.43 (5H, m) The following compounds were obtained substantially in a manner similar to that of Example 54.

EXAMPLE 98 (1S) -N-hydroxy-2- [5- (3-methylphenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide dioxide 120 mg) NMR (DMSO-ds, d): 1.75-2.06 (4H, m), 2.35 (3H, s), 2.95-3.52 (6H, m), 7.13 (HH, d, J = 7.5Hz), 7.20 (HH, d, J = 5Hz), 7.30 (HH, dd, J = 7.5, 7.5Hz), 7.42-7.45 (3H, m), 8 .84 (HH, s) MS (ESI-): 378 (MH) Example 99 1, 1 (2S) -N-hydroxy-2- [5- (4-methylphenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (82 mg) ) NMR (DMSO-ds, d): 1.74-2.04 (4H, m), 2.32 (3H, s), 2.47-2.53 (HH, m), 2.95-3.25 (4H, m), 3.43-3.53 (HH, m ), 7.16 (HH, d, J = 3.0Hz), 7.23 (2H, d, J = 0.7Hz), 7.40 (HH, d, J = 3.0Hz), 7.53 (2H, d, J = 7.0Hz), 6.85 (1H, s) MS (ESI-): 378.0 (MH) Example 100 1, 1-dioxide (2 S) -N-hydroxy-2- [5- (4-ethylphenyl) -2-thienyl] -3 , 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (115 mg) NMR (CDC13, d): 1.24 (3H, t, J = 7Hz), 1.74-1.93 (2H, m), 1.96-2.16 (2H, m), 2.57-2.73 (2H, m), 2.65 (2H, q, J = 7Hz), 2.94-3.15 (4H, m), 7.14-7.24 (4H, m), 7.50 (2H, d, J = 8Hz), 8.52 (H, s) MS (ESI-): 392 (MH) Example 101 (2S) -N-hydroxy-2- [5- (4-methoxyphenyl) -2- thienyl] 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (970 mg) NMR (DMSO-dg, d): 1.72-2.06 (4H, m), 2.34-2.45 (H, m), 2.94-3.26 (4H, m), 3.39-3.56 (HH, m), 3.78 (3H, s), 6.98 (2H, d, J = 7Hz), 7.16 (HH, d, J = 3Hz), 7.34 (HH) , d, J = 3Hz), 7.57 (2H, d, J = 7Hz), 8.85 (H, s), 10.58 (H, s) MS (ESI-): 394 (M- H) Example 102 1,1-Dioxide of (2S) -N-hydroxy-2- [5- (4-hydroxymethylphenyl) -2-thienyl] -3,4,5,6,6-tetrahydro-2H-thiopyran-2 -acetamide (75 mg) NMR (DMSO-ds, d): 1.67-2.08 (4H, m), 2.33-2.48 (HH, m), 2.92-3.28 (4H, m), 3.39-3.54 (HH, m) , 4.50 (2H, d, J = 6Hz), 5.24 (HH, t, J = 6Hz), 7.20 (HH, d, J = 3Hz), 7.36 (2H, d, J = 7Hz), 7.44 (HH, d , J = 3Hz), 7.60 (2H, d, J = 7Hz), 8.86 (OH, s) MS (ESI-): 394 (MH) Example 103 (2S) -N-hydroxy-2 1,1-dioxide - (5- (2-thienyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (130 mg) NMR (DMS0-d6, d): 1.72-2.04 (4H , m), 2.93-3.51 (6H, m), 7.10 (HH, dd, J = 4.5, 4.5Hz), 7.15 (HH, d, J = 4.0Hz), 7.26 (HH, d, J = 4.0Hz) , 7.29 (HH, d, J = 4.5Hz), 7.53 (HH, d, J = 4.5Hz), 8.32 (HH, s) MS (ESI-): 370 (MH) Example 104 1,1-dioxide ( 2S) -N-hydroxy-2- (5- (2-furyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (12 mg) NMR (CDC13, d): 1.80-1.97 (2H, m), 2.00-2.25 (2H, m), 2.56-2.69 (HH, m), 2.74-2.89 (HH, m), 2.96-3.20 (4H, m) ), 6.43-6.47 (IH, m), 6.52-6.56 (IH, m), 7.15-7.22 (12H, m), 7.39-7.44 (IH,), 8.12 (IH, br s) MS (ESI-): 354 (MH) EXAMPLE 105 1,1-Dioxide (2S) -N-hydroxy -2 - [5- (4-me ti Icarbamoyl phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H -thiopyran-2-acetamide (46 mg) NMR (DMSO-ds, d): 1.68-2.10 (4H,), 2.33-2.48 (ÍH, m), 2.79 (3H, d, J = 4Hz), 2.92-3.32 (4H, m), 3.40-3.57 (HH,), 7.26 (HH, d, J = 3Hz), 7.60 (HH, d, J = 3Hz), 7.74 (2H, d, J = 8Hz), 7.88 (2H) , d, J = 8Hz), 8.50 (HH, m) MS (ESI-): 421 (MH) Example 106 1, 1-dioxide (2S) -N-hydroxy-2 - [5- (4-et ilcarbamoyl phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (740 mg) NMR (DMSO-ds, d): 1.13 (3H, t, J = 7.5Hz) , 1.75- 2.05 (4H, m), 2.36-2.45 (HH,), 2.95-3.03 (2H, m), 3.13-3.47 (5H, m), 7.24 (HH, d, J = 5.0Hz), 7.60 ( ÍH, d, J = 5.0Hz), 7.73 (2H, d, J = 9.0Hz) , 7.87 (2H, d, J = 9.0Hz), 8.51 (H, t, J = 3.0Hz) MS (ESI-): 435.2 (MH) Example 107 1, 1-dioxide (2S) -N-hydroxy- 2- [5- (3-acetylaminophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (2 g) NMR (DMSO-d6, d): 1.74-2.01 ( 4H, m), 2.06 (3H, s), 2.35-2.46 (HH, m), 2.94-3.50 (5H, m), 7.20 (HH, d, J = 3.0Hz), 7.33 (2H, d, J = 3.0Hz), 7.39 (HH, d, J = 3.0Hz), 7.44-7.49 (HH, m), 7.94 (HH, s) MS (ESI-): 421.1 (MH) Example 108 1,1-Dioxide Hydrochloride of (2S) -N-hydroxy-2- [5- (3-aminophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (87 mg) NMR (DMS0- d6, d): 1.69-2.09 (4H, m), 2.34-2.56 (ÍH, m), 2.95-3.07 (2H, m. ), 3.11-3.32 (2H, m), 3.40-3.57 (HH, m), 7.17 (HH, d, J = 8Hz), 7.24 (HH, d, J = 3Hz), 7.42-7.60 (4H, m) , 10.63 (1H, s) MS (ESI-): 379 (MH) Example 109 (2S) -N-hydroxy-2 - [5- (3-ethylcarbamoylaminophenyl) -2-thienyl 1,1-dioxide) -3 , 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide NMR (DMS0-d5, d): 1.06 (3H, t, J = 7.2Hz), 1.69-2.09 (4H, m), 2.31-2.53 ( ÍH, m), 2.93-3.55 (7H, m), 6.14 (ÍH, t, J = 4.5Hz), 7.12-7.30 (4H,), 7.38 (ÍH, d, J = 4.5Hz), 7.84 (ÍH, s), 8.56 (OH, s), 8.72-8.95 (OH, m), 10.60 (OH, s) MS (ESI-): 450 (MH) Example 110 (2S) -N-hydroxy 1,1-dioxide -2- (5- (3-ethyloxycarbonylaminophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (82 mg) NMR (DMS0-d6, d): 1.70-2.07 ( 4H, m), 2.34-2.53 (HH, m), 2.94-3.08 (2H, m), 3.10-3.27 (2H,), 3.30-3.55 (HH, m), 3.69 (3H, s), 7.20 (HH) , d, J = 3.5Hz), 7.27-7.41 (4H, m), 7.83 (HH, s), 9.76 (HH, s) MS (ESI +): 456 (M + H + NH3) Example 111 1.1- (2S) -N-hydroxy-2- [ 5- (3-carbamoi lamino) phenyl) -2-thienyl] -3,, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (45 mg) NMR (DMSO-ds, d): 1.70-2.08 (4H , m), 2.32-2.55 (ÍH, m), 2.93-3.07 (2H, m), 3.09-3.30 (2H, m), 3.39-3.55 (ÍH, m), 5.90 (2H, s), 7.16- 7.23 (2H,), 7.24-7.39 (2H,), 7.37 (IH, d, J = 3.5Hz), 7.78 (IH, s), 8.66 (IH, s), 8.84 (IH, s) MS (ESI-) : 4.22 (MH) Example 112 (2S) -N-hydroxy-2- [5- (3-methylcarbamoylaminophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide 1, 1-dioxide (77 mg) NMR (DMS0-d6, d): 1.74-2.05 (4H, m), 2.38-2.46 (HH, m), 2.66 (3H, d, J = 4.0Hz), 2.95-3.26 ( 4H, m), 3.42-3.52 (HH, m), 6.06 (HH, q, J = 4.0Hz), 7.17-7.20 (2H, m), 7.22-7.26 (2H, m), 7.36 (1H, d, J = 3.5Hz), 7.82 (HH, s), 8.65 (HH, s), 8.83 (HH, s) MS (ESI-): 436.2 (MH) Example 113 To a solution of cyclic 1,3-propandiol ester of pyridin-3-boronic acid (130 mg) in degassed N, N-dimethylformamide (0.5 ml) was added a suspension of tetrakis (triphenylphosphine) -palladium (103 mg) in N, degassed N-dimethylformamide (2.5 ml), a solution of sodium carbonate (424 mg) in degassed water (1 ml) and (2S) -N- [2- (2- (5-bromo-2-) crowns) thienyl) -1,1-dioxo-3,4,5,6-tetrahydro-2H-thiopyran-2-yl] acetyl] hydroxylamine trityl (b) (4 mmol, 10.0 μmol / crown) under a nitrogen atmosphere. After heating the resulting mixture for 5 48 hours at 60 ° C, the crowns were washed successively with Degassed N, N-dimethylformamide, a solution of sodium diethyldithiocarbamate (500 mg) and diisopropylethylamine (0.5 ml) in N, N-dimethylformamide (100 ^^ ml), N, N-dimethylformamide, methyl sulfoxide, water, methanol and dichloromethane. The crowns were treated with 5% trifluoroacetic acid in dichloromethane for 1 hour at room temperature and removed from the solution. Then, the solution was evaporated under a stream of nitrogen, the residue was purified by reverse phase HPLC (0.1% trifluoroacetic acid in acetonitrile, gradient 0-20%) to form 1,1-dioxide (2S) -N- hydroxy-2- [5- (3-pyridyl) - ^^ 2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (10 mg) as a powder. NMR (DMSO-d6, d): 1.25-2.05 (4H, m), 2.87-2.93 20 (HH, m) 2.97-3.50 (5H, m), 7.28 (HH, d, J = 4.0Hz), 7.53- 7.58 (HH, m), 7.65 (HH, d, J = 4.0Hz), 8.16 (HH, d, J = 7.5Hz), 8.56 (HH, br), 8.95 (HH, br) MS (ESI-): 365.0 (MH) 5 Example 114 (2 S) -N- (2-tetrahydropyranyloxy) -2- [5- (3-methylcarbamoylaminophenyl) -2-thienyl] -3,4,5-6-1,1-dioxide tetrahydro-2H-thiopyran-2-acetamide (132 mg) NMR (CDC13, d): 1.45 (4H, br), 1.62-1.66 (2H, m), 1.93 (2H, br), 2.07-2.17 (2H,) , 2.77- 2.81 (5H, m), 2.98-3.03 (HH, m), 3.10-3.15 (3H, m), 3.32-3.50 (HH, m), 3.70-3.78 (HH, m), 4.59 (HH x 1/2, s), 4.83 (HH x 1/2, s), 7.00 (HH, d, J = 3.5Hz), 7.07-7.08 (HH,), 7.12-7.21 (4H,), 7.30-7.40 ( 2H, m), 9.16 (HH x 1/2, s), 9.35 (1H x 1/2, s) MS (ESI-): 520.2 (MH) The following compounds were obtained in substantially the same manner as that of the Example 89. Example 115 1 (1 S) -N- (2-tetrahydropyranyloxy) -2- [5- (3-methylphenyl) -2-thienyl] -3, 4-dioxide , 5,6-tetrahydro-2H-thiopyran-2-acetamide (200 mg) NMR (CDCl 3, d): 1.40-1.73 (10H, m), 2.37 (3H, s), 2.69-2.88 (2H, m), 3.06-3.16 (4H, m), 3.30-3.45 (HH, m), 3.61-3.75 (2H, rti), 7.11 (HH, d, J = 7.5Hz), 7.24-7.28 (3H, m), 7.38- 7.41 (2H,) Example 116 (2 S) -N- (2-tetrahydropyranyloxy) -2- [5- (4-methylphenyl) 2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran- 2-acetamide 1,1-dioxide (142 mg) NMR (CDC13, d): 1.43 (2H, br), 1.65-1.69 (2H, m), 1.95 (2H, br), 2.07-2.18 (2H, m) , 2.37 (3H, 3), 2.63-2.80 (2H, m), 3.06 (2H, br s), 3.10-3.16 (2H, m), 3.40-3.50 (2H, m), 3.58- 3.76 (2H , m), 4.53 (HH x 1/2, s), 4.80 (HH x 1/2, s), 7.15-7.24 (4H, m), 7.46 (2H, d, J = 8.0Hz), 7.39 (HH) x 1/2, s), 8.06 (HH x 1/2, s) MS (ESI-): 462.1 (MH) Example 117 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4-Ethylphenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide NMR (CDCl 3, d): 1.25 (3H, t, J = 8Hz), 1.35 -1.76 (6H,), 1.87-2.00 (2H, m), 2.04-2.23 (2H, m), 2.60-2.91 (4H, m), 3.00-3.19 (4H, m), 3.27-3.50 (H, m), 3.60-3.77 (H, m), 4.53, 4.71 (H, s), 7.15- 7.28 (4H,), 7.51 (2H, d, J = 8Hz), 8.10, 8.25 (OH, s) MS (ESI +): 478 (M + H) Example 118 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4-methoxyphenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (1.85 g) NMR (CDCl 3, d): 1.36-1.82 (6H, m), 1.98-2.02 (2H, m), 2.10-2.25 (2H, m), 2.62-2.88 (2H, m), 2.98-3.20 (4H, m), 3.26-3.50 (2H , m), 3.57-3.72 (HH, m), 3.83 (3H, s), 6.90 (2H, d, J = 8Hz), 7.13, 7.15 (HH, d, J = 3Hz), 7.22, 7.24 (HH, d, J = 3Hz), 7.52 (2H, d, J = 8Hz), 8.11, 8.25 (H, s) MS (ESI-): 478 (MH) Example 119 1, (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4-hydroxymethylphenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-dioxide acetamide (161 mg) NMR (CDCI3, d): 1.36-1.78 (6H, m), 1.85-2.03 (2H, m), 2.06-2.55 (2H, m), 2.66-2.93 (2H, m), 2.98- 3.21 (4H, m), 3.26-3.50 (HH, m), 3.62-3.73 (HH, m), 4.52, 4.82 (HH, m), 4.70 (HH, s), 7.22-7.30 (HH, m), 7.35 (2H, d, J = 8Hz), 7.42-7.62 (HH, m), 7.57 (2H, d, J = 8Hz), 8.25, 8.35 (HH, s) MS (ESI-): 478 (MH) Example 120 1, 1 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (2-t-thienyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran 2-acetamide (200 mg) NMR (CDCI3, d): 1.41-1.75 (10H, m), 2.65-2.82 (2H,), 3.04-3.17 (4H, m), 3.30-3.74 (3H, m), 7.00 -7.02 (HH, m), 7.11-7.13 (HH, m), 7.17-7.19 (3H, m) MS (ESI-): 454 (MH) Example 121 1, 1-dioxide (2S) -N- ( 2-tetrahydropyranyloxy) -2- [5- (2-furyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2H-acetamide (95 mg) NMR (CDC13, d): 1.41 -1.77 (6H, m ), 1.85-2.00 (2H, m) 2.03-2.25 (2H, m), 2.61-2.91 (2H, m), 3.00-3.06 (2H, m), 3.07-3.19 (2H, m), 3.28-3.53 ( ÍH, m), 3.61-3.75 (ÍH, m), 4.51 (0.5H, s), 4.80 (0.5H, s), 6.42-6.47 (ÍH, m), 6.50-6.56 (ÍH, m), 7.17- 7.24 (2H, m), 7.38-7.42 (HH, m), 7.93 (0.5H, s), 8.09 (0.5H, s) MS (ESI-): 438 (MH) Example 122 1,1-dioxide ( 2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4-carboxyphenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (910 mg) NMR ( CDCI3, d): 1.36-1.73 (6H, m), 1.85-2.25 (4H,), 2.76-2.88 (2H, m), 3.02-3.25 (4H, m), 3.28-3.53 (HI, m), 3.69 -3.61 (HH, m), 4.56, 4.87 (HH, s), 7.57 (HH, d, J = 8Hz), 7.36-7.44 (HH, m), 7.72-7.83 (2H, m), 8.00 ( 2H, d, J = 8Hz) MS (ESI-): 492 (MH) Example 123 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- (5- (4-ethocarbamoyl phenyl) -2-thienyl] -3, 4, 5, 6-tetrahydro-2 H-thiopyran-2-acetamide (964 mg) NMR (CDC13, d): 1.28 (3H, t, J = 7.0Hz), 1.44-1.55 (4H,), 1.64-1.68 (2H, m), 1 .95 (2H, br), 2.06-2.23 (2H, m), 2.67-2.91 (2H, m), 3.01- 3.16 (4H, m), 3.27-3.33 (ÍH, m), 3.46-3.55 (2H, ), 3.62-3.65 (HH, m), 4.50 (HH x 1/2, s), 4.82 (HH x 1/2, s), 7.28 (HH, d, J = 4.0Hz), 7.33 (HH, d , J = 4.0Hz), 7.62 (2H, d, J = 8.0Hz), 8.19 (HH x 1/2, d, J = 8.0Hz), 7.75 (2H, d, J = 8.0Hz), 8.19 (HH) x 1/2, s), 8.27 (HH x 1/2, s) MS (ESI-): 519.2 (MH) Example 124 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3-acetylaminophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H thiopyran-2-acetamide (2.63 g) NMR (CDCl 3, d): 1.43 (2H, br), 1.55 -1.64 (4H, m), 1.93 (2H, br), 2.04-2.15 (2H, m), 2.19 (3H, s), 2.80-2.85 (2H, m), 3.02-3.16 (4H, m), 3.44 -3.48 (HH, m), 3.66-3.73 (HH, m), 4.55 (HH x 1/3, s), 4.85 (HH x 2/3, s), 7.08-7.11 (HH, m), 7.16-7.23 (3H, m), 7.38 (HH, brs), 7.57 (HH, d, J = 7.0Hz), 7.94 (HH, s), 8.93 (HH x 1/3, s), 9.02 (HH) x 2/3, s) MS (ESI-): 505.4 (MH) Example 125 1, 1-dioxide (2S) -N- (2-tetrahydropy) ranyloxy) -2- [5- (3-aminofenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (214 mg) NMR (CDC13, d): 1.36- 1.80 (6H, m), 1.84-2.25 (4H, m), 2.61-2.92 (2H, m), 2.98-3.20 (4H, m), 3.27-3.89 (4H, m), 4.54 (0.5H, s) , 4.81 (0.5H, s), 6.62 (HH, dd, J = 2.3, 8Hz), 6.91 (1H, s), 6.99 (HH, d, J = 8Hz), 7.15 (HH, t, J = 8Hz) , 7.20-7.29 (2H, m), 7.98 (0.5H, s), 8.15 (0.5H, s) MS (ESI-): 463 (MH) Example 126 2- (5-bromo-2-thienyl) was obtained 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-t-butyl acetate (199 g) in substantially the same manner as that of Example 93. NMR (CDCl 3, d): 1.34 (9H, s) , 1.46-1.91 (5H, m), 2.10-2.22 (HH, m), 2.49-2.62 (2H, m), 2.66 (HH, d, J = 13.2Hz), 2.75 (HH, d, J = 13.2Hz ), 6.74 (HH, d, J = 3.9Hz), 7.45 (HH, d, J = 3.9Hz) Example 127 (2S) -2- (5-bromo-2-thienyl) -3,1-dioxide , 4, 5, 6-tetrahydro-2H-thiopyran-2-N- [(R) -1-phenylethyl] acetamide (78 g) was partitioned between ethyl acetate (500 ml) and IN aqueous hydrochloric acid (300 ml). ), the separated organic phase was washed with IN aqueous hydrochloric acid (100 ml) and brine (100 ml), dried over sodium sulfate and concentrated in vacuo to form (2S) -2- (5-bromo-2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran acid 1,1-dioxide. -2-acetic (57.5 g) as a solid. Melting point: 189 ° C (dec.) NMR (DMSO-dg, d): 1.74-1.87 (4H, m), 2.30-2.37 (H, m), 3.07-3.56 (5H,), 7.02 (H, d, J = 4.2Hz), 7.21 (H, d, J = 4.2Hz) Example 128 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4-methylcarbamoyl phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (68 mg) was obtained in substantially the same manner as that of Example 32. NMR (DMSO-ds, d): 1.35-1.64 (6H, m), 1.71-2.08 (4H, m), 2.36-2.53 (ÍH, m), 2.79 (3H, d, J = 4Hz), 2.88-3.32 (4H, m), 3.40-3.53 (2-H, 'm), 3.74-3.92 (HH, m), 4.45, 4.75 (1H, s), 7.22-7.30 (HH, m), 7.55-7.64 (HH, m), 7.74 (2H, d) , J = 8Hz), 7.88 (2H, d, J = 8Hz), 8.50 (IH, d, J = 4Hz), 11.25 (IH, s) MS (ESI-): 505 (MH) Example 129 A mixture of 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3-aminophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2- acetamide (110 mg) in dichloromethane (1.5 ml) was added a solution of ethylisocyanate (21.9 mg) in dichloromethane (0.5 ml) with cooling with ice. The mixture was allowed to warm to room temperature and was stirred for 3 hours. The resulting mixture was purified by chromatography on silica gel (methanol in chloroform, gradient 0.5 to 3%) to form 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- ethylcarbamoylaminophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (100 mg) as an amorphous solid. NMR (CDC13, d): 1.08-1.18 (3H,), 1.38-1.75 (6H, m), 1.86-2.00 (2H, m), 2.02-2.24 (2H, m), 2.76-2.90 (2H,), 2.96-3.17 (4H, m), 3.20-3.55 (3H, m), 3.70-3.65 (HH, m), 4.61 (0.5H, s), 4.84 (0.5H, s), 5.25-5.40 (HH, m ), 6.95-7.34 (5H, m), 7.36-7.50 (ÍH, m), 9.13 (0.5H, s), 9.35 (0.5H, s) MS (ESI-): 534 (MH) Example 130 To a mixture of (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3-aminophenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-1,1-dioxide -acetamide (110 mg) and pyridine (28.1 mg) in dichloromethane (1.5 ml) was added a solution of methyl chloroformoate (26.8 mg) in dichloromethane (0.5 ml) with ice cooling. The mixture was allowed to warm to room temperature and was stirred for 3 hours. The resulting mixture was washed with 0.5% aqueous citric acid and brine, dried over sodium sulfate and concentrated in vacuo. The residue obtained was purified by chromatography on silica gel (methanol in chloroform, gradient 0.5 to 3%) to form 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- methoxycarbonyl-aminophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (101 mg) as an amorphous solid. NMR (CDC13, d): 1.35-1.56 (4H, m), 1.59-1.75 (2H, m), 1.86-2.00 (2H, m), 2.05-2.26 (2H, m), 2.63-2.93 (2H, m) ), 3.01-3.17 (4H, m), 3.27-3.51 (HH, m), 3.58-3.74 (HH, m), 3.79 (3H, s), 4.54 (0.5H, s), 4.82 (0.5H, s) ), 6.74 (ÍH, br s), 7.15-7.21 (ÍH, m), 7.23- 7.37 (4H, m), 7.62 (ÍH, br s), 8.10 (0.5H, s), 8.24 (0.5H , s) MS (ESI-): 521 (MH) The following compound was obtained in substantially the same manner as that of Example 129. Example 131 1, 1 (2S) -N- (2-tetrahydropyranyloxy) -2-dioxide - [5- (3-aminocarbamoylphenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (170 mg) NMR (DMSO-d6, d): 1.36-1.65 (6H , m), 1.69-2.10 (4H, m), 2.34-2.48 (HH, m), 2.89-3.32 (4H, m), 3.39-3.54 (2H, m), 3.72-3.91 (HH, m), 4.43 (0.5H, s), 4.75 (0.5H, s), 5.90 (2H, s), 7.16-7.30 (4H, m), 7.32-7.49 (H, m), 7.79 (H, s), 8.66 (H) , s) MS (ESI-): 506 (MH) Example 132 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4-fluorophenyl) 1,1-dioxide was obtained -2-thienyl] -2, 3, 4, 5-tetrahydrothiophene-2-acetamide (272 mg) in a manner similar to that of Example 32. NMR (CDC13, d): 1.39-1.84 (6H, m), 2.27 -2.41 (2H, m) 2.82-3.00 (4H, m), 3.13-3.25 (2H, m), 3.35-3.63 (HH, m), 3.68-3.80 (HH, m), 4.55-4.64 (0.5H), m), 4.81-4.89 (0.5H, m), 7.03-7.11 (2H, m), 7.13-7.40 (2H, m), 7.49-7.58 (2H, m), 8.20 (0.5H, s) , 8.30 (0.5H, s) MS (ESI-): 452 (MH) The following compounds were obtained in substantially the same manner as that of Example 54. Example 133 (2S) -N-hydroxy 1,1-dioxide - 2 - [5- (3-Etoxyacetylaminophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (4.62 g) NMR (DMSO-ds, d): 1.20 (3H , t, J = 7Hz), 2.35-2.48 (HH, m), 2.94-3.28 (4H, m), 3.42-3.53 (HH, m), 3.58 (2H, q, J = 7Hz), 4.04 (2H, s), 7.21 (ÍH, d, J = 3Hz), 7.32-7.44 (3H, m), 7.57-7.63 (ÍH, m), 8.03 (ÍH, s), 8.65 (ÍH, br), 9.81 (ÍH, s) MS (ESI-): 465 (MH) Example 134 (2 S) -N-hydroxy-2- [5- (3-propionyl aminophenyl) -2-thienyl] -3,4-dioxide, 5,6-tetrahydro-2H-thiopyran-2-acetamide (76 mg) NMR (DMSO-dg, d): 1.09 (3H, t, J = 7Hz), 2.35 (2H, q, J = 7Hz), 2.37- 2.48 (HH, m), 2.90-3.52 (5H, m), 7.21 (HH, d, J = 3Hz), 7.28-7.53 (5H, m), 8.00 (HH, s), 9.98 (HH, s), 10 61 (OH, s) MS (ESI-): 435 (MH) EXAMPLE 135 1, 1-Dioxide (2S) -N-hydroxy-2 - [5- (3-propylaminocarbonylaminophenyl) -2-thienyl) -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (75 mg) NMR (DMSO-ds, d): 0.88 (3H, t, J = 7Hz), 1.44 (2H, q, J = 7Hz), 1.68-2.10 (4H, m), 2.34-2.48 (HH, m), 2.90-3.58 (7H, m), 6.22 (HH, br), 7.11-7.30 (4H, m), 7.48 (HH, d, J = 3Hz), 7.84 (HH, s), 8.60 (HH, s), 10.61 (HH, s) MS (ESI-): 464 (MH) Example 136 1, 1-dioxide (2S) -N-hydroxy -2- [5- (3-butyral lamino phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (79 mg) NMR (DMSO-ds, d): 0.92 (3H, t, J = 7Hz), 1.55-1.68 (2H, m), 1.69-2.10 (4H, m), 2.30 (2H, t, J = 7Hz), 2.35-2.48 (ÍH,), 2.92-3.65 (5H, m), 7.20 (HH, d, J = 3Hz), 7.34 (2H, d, J = 3Hz), 7.40 (HH, d, J = 3Hz), 7.44-7.53 (HH, m), 8.00 (1H, s) MS (ESI-): 449 (MH) Example 137 (2S) -N-hydroxy-2- [5- (3- (2-methoxyethoxycarbonyllamino) phenyl) -2-dioxide) -2 -thienyl] -3, 4, 5, 6-tetrahydro -2H-thiopyran-2-acetamide (64 mg) NMR (DMSO-d6, d): 1.70-2.11 (4H, m), 2.34-2.50 (H, m), 2.92-3.26 (4H, m), 3.29 ( 3H, s), 3.40-3.66 (3H, m) 4.15-4.26 (2H, m), 7.20 (IH, d, J = 3Hz), 7.26-7.42 (4H, m), 7.85 (IH, s) , 8.84 (H, s), 9.87 (H, s), 10.60 (H, s) MS (ESI-): 481 (MH) Example 138 (2S) -N-hydroxy-2 1,1-dioxide - [5- (3- (2-methoxycarbonylaminoacetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (58 mg) NMR (DMSO-ds, d): 1.69-2.07 (4H, m), 2.32-2.48 (HH, m), 2.92-3.50 (5H, m), 3.56 (3H, s), 3.80 (2H, d, J = 8Hz), 7.19 (HH, d , J = 3Hz), 7.30-7.52 (5H, m), 7.97 (OH, s), 8.82 (OH, s) MS (ESI-): 494 (MH) Example 139 1, 1-dioxide (2S) - N-hydroxy -2 - [5- (3- (phenoxyacetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (3.8 g) JNMR (DMSO-dg , d): 1.70-2.09 (4H, m), 2.35-2.50 (ÍH,), 2.92-3. , 55 (5H, m), 4.72 (2H, s), 6.94-7.05 (3H,), 7.21 (HH, d, J = 3Hz), 7.28-7.44 (5H, m), 7.52-7.60 (HH, m ), 8.03 (HI, s), 8.84 (HH, s), 10.21 (HH, s), 10.60 (HH, s) MS (ESI-): 513 (MH) Example 140 1,1-dioxide (2S) -N-hydroxy-2- [5- (3- (propoxyacetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (2.28 g) NMR (DMSO-ds , d): 0.91 (3H, t, J = 8Hz), 1.54-1.67 (2H, m), 1.70-2.11 (4H, m), 2.36-2.49 (ÍH, m), 2.94-3.29 (4H, m) , 3.43-3.58 (HH, m), 3.48 (2H, t, J = 8Hz), 4.05 (2H, s), 7.21 (HH, d, J = 3Hz), 7.32-7.45 (3H, m), 7.54- 7.62 (ÍH, m), 8.03 (ÍH, s), 8.85 (ÍH, s), 9.81 (ÍH, s), 10.60 (ÍH, s) MS (ESI-): 479 (MH) Example 141 1,1- (2S) -N-hydroxy-2- [5- [3- (2-propen-l-yloxy) acetylamino] phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran dioxide -2-acetamide (9.32 g) NMR (DMSO-d6, d): 1.70-2.09 (4H, m), 2.35-2.56 (HH, m), 2.94-3.08 (2H, m), 3.10-3.29 (2H, ), 3.30-3.55 (ÍH, m), 4.07 (2H, s), 4.10 (2) H, d, J = 6Hz), 5.22 (HH, d, J = 9Hz), 5.34 (HH, d, J = 15Hz), 5.89-6.04 (HH, m), 7.21 (HH, d, J = 3.5Hz ), 7.31-7.44 (3H, m), 7.55- 7.61 (HH, m), 8.03 (HH), s), 8.85 (OH, br s), 9.86 (OH, s), 10.6 (OH, br s) MS (ESI-): 477 (MH) Example 142 (2S) -N hydroxy-2- [5- [4- (5-oxazolyl) phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (331 mg) NMR (DMSO-d6, d): 1.72-2.10 (4H, m), 2.36-2.49 (HH, m), 2.95-3.09 (2H, m), 3.11-3.30 (2H, m), 3.42-3.56 (HH, m), 7.24 ( HH, d, J = 3.9Hz), 7.57 (HH, d, J = 3.9Hz), 7.76 (HH, s), 7.77 (4H, s), 8.48 (HH, s) MS (ESI-): 431 ( MH) Example 143 (2S) -N-hydroxy-2- [5- (3- (n-butyloxyacetylamino) phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H 1,1-dioxide -thiopyran-2-acetamide (90 mg) NMR (DMSO-ds, d): 0.92 (3H, t, J = 7.0Hz), 1.47 (2H, tq, J = 7.0, 7.0Hz), 1.60 (2H, dd , J = 7.0, 7.0Hz), 1.74-2.06 (4H, m), 2.37-2.47 (HH, m), 2.96-3.30 (4H, m), 3.38-3.45 (HH, m), 3.52 (2H, t , J = 7.0Hz), 4.05 (2H, s), 7.22 (HH, d, J = 4.0Hz), 7.32-7.37 (2H, m), 7.41 (HH, d, J = 4.0Hz), 7.55-7.60 (ÍH, m), 8.02 (ÍH, s), 8.84 (ÍH, s), 9.80 (ÍH, s), 10.59 (HH, s) MS (ESI-): 493.2 (MH) Example 144 1, 1-dioxide (2 S) -N-hydroxy-2- [5- (3-ethoxycarbonylaminoacetylamino) phenyl] -2-thienyl] - 3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (2.3 g). NMR (DMSO-ds, d): 1.18 (3H, t, J = 7.0Hz), 1.74- 2.05 (4H, m), 2.36-2.45 (HI, m), 2.95-3.26 (4H, m), 3.40- 3.53 (ÍH,), 3.79 (2H, d, J = 6.0Hz), 4.02 (2H, q, J = 7.0Hz), 7.21 (ÍH, d, J = 4.0Hz), 7.35-7.40 (3H, m) , 7.40 (HH, d, J = 4.0Hz), 7.45-7.49 (HH, m), 7.97 (HH, s), 8.84 (HH, s), 10.08 (HH, s) MS (ESI-): 508.3 ( MH) Example 145 (2S) -N-hydroxy-2- [5- (3- (2-chloroethylaminocarbonyllamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydroxy-1,1-dioxide 2H-thiopyran-2-acetamide (72 mg) NMR (DMSO-dg, d): 1.72-2.04 (4H, m), 2.36-2.45 (H, m), 2.93-3.23 (4H, m), 3.39-3.46 (3H, m), 3.67 (2H, t, J = 6.0Hz), 6.44 (IH, t, J = 6.0Hz), 7.17-7.30 (4H, m), 7.38 (IH, d, J = 4.0Hz) , 7.84 (H, s), 8.81 (H, s), 8.84 (H, s) MS (ESI-): 484.3 (MH) Example 146 (2S) -N-hydroxy-2- [1,1-dioxide] 5- (3- (3-methoxypropionylamino) -phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (3.4 g) NMR (DMSO-d6, d): 1.72 -2.05 (4H,), 2.38-2.41 (ÍH,), 2.56 (2H, J = 6.0H z), 2.95-3.21 (4H, m), 3.27 (3H, s), 3.36-3.52 (HH, m), 3.64 (2H, t, J = 6.0Hz), 7.20 (HH, d, J = 4.0Hz ), 7.31-7.36 (2H, m), 7.40 (IH, d, J = 4.0Hz), 7.45-7.49 (IH, m), 8.01 (IH, s), 10.07 (IH, s), 10.60 (IH, s) MS (ESI-): 479.2 (M-H + Na) EXAMPLE 147 1, 1-Dioxide of (2S) -N-hydroxy-2- [5- (3-. { me toxiace ti lamino) phenyl} -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (2.5 g) NMR (DMSO-d6, d): 1.74-2.06 (4H, m), 2.37-2.48 (H) , m), 2.95-3.26 (4H, m), 3.41 (3H, s), 3.43-3.53 (HH, m), 4.02 (2H, s), 7.20 (HH, d, J = 4.0Hz), 7.32- 7.38 (2H, m), 7.42 (HH, d, J = 4.0Hz), 7.58-7.63 (HH, m), 8.04 (HH, s), 8.84 (HH, s), 9.81 (HH, s), 10.60 (HH, s) MS (ESI-): 451.2 (MH) EXAMPLE 148 1,1-Dioxide (2S) -N-hydroxy -2 - [5- (3-hydroxymethylphenyl) -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (60 mg) NMR (DMSO-ds, d): 1.71-2.08 (4H, m), 2.37-2.46 (HH,), 2.95-3.54 (5H ,), 4.54 (2H, d, J = 5.5Hz), 5.29 (HH, dd, J = 5.5, 5.5Hz), 7.21 (HH, d, J = 4.0Hz), 7.25 (HH, d, J = 8.0) Hz), 7.38 (HH, dd, J = 8.0, 8.0Hz), 7.46 (HH, d, J = 4.0Hz), 7.53 (HH, d, J = 8.0Hz), 7.59 (HH, s), 8.85 ( HH, s), 10.6 (HH, s) MS (ESI-): 394 (MH) Example 149 (2S) -N-hydroxy-2- [5- (4- (cis-1, 2-dihydroxyethyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran -2-acetamide (100 mg) NMR (DMSO-d6, d): 1.73-2.07 (4H, m), 2.35-2.46 (HH, m), 2.95-3.50 (5H, m), 4.51-4.56 ( ÍH,), 4.70-4.80 (ÍH, br), 5.24-5.35 (ÍH, br), 7.20 (ÍH, d, J = 4.0Hz), 7.39 (2H, d, J = 8.0Hz), 7.44 (ÍH, d, J = 4.0Hz), 7.58 (2H, d, J = 8.0Hz), 8.83 (OH, s), 10.58 (OH, s) MS (ESI-): 424 (MH) Example 150 1, 1-dioxide of (2S) -N-hydroxy-2- [5- (3- (methylaminocarbonyloxymethyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-acetamide (100 mg) NMR (DMSO -d6, d): 1.10-2.06 (4H,), 2.35-2.46 (ÍH, m), 2.59 (3H, d, J = 5.0Hz), 2.96-3.54 (5H, m), 5.05 (2H, m), 7.22 (ÍH, d, J = 4.0Hz), 7.29 (ÍH, d, J = 5.0Hz), 7.42 (HH, dd, J = 8.0, 8.0Hz), 7.49 (HH, d, J = 4.0Hz), 7.59-7.61 (HH, m), 6.84 (HH, br), 10.59 ( ÍH, br) MS (ESI-): 4.51 (MH) Example 151 (2S) -N-hydroxy-2- [5- (4- (2-methyl-aminocarbonyletenyl) phenyl) -2-thionyl 1,1-dioxide ] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (170 mg) NMR (DMSO-ds, d): 1.72-2.09 (4H, m), 2.38-2.48 (H, m), 2.71 (3H, d, J = 5Hz), 2.98-3.51 (5H, m), 6.63 (HH, d, J = 15Hz), 7.23 (HH, d, J = 4Hz), 7.42 (HH, d, J = 15Hz), 7.55 (HH, d, J = 4Hz), 7.60 (2H, d, J = 8.4Hz), 7.69 (2H, d, J = 8.4Hz), 8.05 (HH, d, J = 5Hz), 10.60 (HH, s) MS (ESI-): 447 (MH) Example 152 (2S) -N-hydroxy-2- [5- (4- (2-ethylamino non-charcoal) -2H-dioxide thiopyran-2-phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2-acetamide (200 mg) NMR (DMSO-d6, d): 1.08 (3H, t, J = 7.2Hz), 1.73- 2.12 (4H, m), 2.39-2.48 (ÍH, m), 2.96-3.05 (2H, m), 3.11-3.5 4 (5H, m), 6.63 (HH, d, J = 15Hz), 7.24 (HH, d, J = 4Hz), 7.41 (HH, d, J = 15Hz), 7.55 (HH, d, J = 4Hz) , 7.60 (2H, d, J = 8.4Hz), 7.69 (2H, d, J = 8.4Hz), 8.10 (IH, dd, J = 7.2, 7.2Hz), 10.6 (IH, s) MS (ESI-) : 461 (MH) EXAMPLE 153 (2S) -N-Hydroxy-2- [5- (3- (i-sopropi-laminocarbonyl-lamino) phenyl) -2-thienyl] -3, 4, 5, 6-dioxide -tetrahydro-2H-thiopyran-acetamide (82 mg) NMR (DMSO-ds, d): 1.10 (6H, d, J = 8Hz), 1.65-2.11 (4H, m), 2.30-2.45 (H, m), 2.85-3.26 (4H, m), 3.36-3.56 (ÍH, rti), 3.65-3.88 (ÍH, m), 6.08 (ÍH, br s), 7.07-7.45 (6H, m), 7.84 (ÍH, s) , 8.50 (OH, s), 10.62 (OH, s) MS (ESI-): 464 (MH) Example 154 1,1-Dioxide hydrochloride (2S) -N-hydroxy-2- (5- [3- [(2-Hydroxyethylamino) -acetylamino] phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopra-ran-2-acetamide (82 mg) NMR (DMSO-d6, d): 1.70 -2.10 (4H, m), 2.32-2.53 (ÍH, m), 2.94-3.06 (2H, m), 3.09-3.20 (2H, m), 3.21-3.30 (2H, m), 3.40-3.86 (3H, m), 3.98-4.05 (2H, m), 7.23 ( H, d, J = 3.5Hz), 7.37-7.53 (4H, m), 7.93-8.00 (2H, m), 8.93-9.07 (2H, s) MS (ESI +): 482 (M + H) Example 155 1,1-Dioxide (2S) hydrochloride-N-hydroxy-2- [5- [3- [(4-morpholino) acetylamino] -phenyl] -2-thienyl] -3,4,5,6-tetrahydro -2H-thiopyran-2-acetamide (75 mg) NMR (DMSO-dg, d): 1.70-2.10 (4H, m), 2.32-2.52 (H, m), 2.90-3.06 (2H, m), 3.09- 3.37 (4H, m), 3.41-3.58 (5H, m), 3.62-4.03 (2H, m), 4.25 (2H, s), 7.23 (ÍH, d, J = 3.5Hz), 7.40- 7.54 (5H, ), 8.03 (H, s) MS (ESI +): 508 (M + H) Example 156 (2S) -N-hydroxy-2- [5- (3- (4-methoxy-phenyl) -acetylamino] 1,1-dioxide ) -phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (105 mg) NMR (DMSO-d6, d): 1.70-2.08 (4H, m), 2.34 -2.48 (HH, m), 2.92-3.30 (4H, m), 3.42-3.54 (HH,), 3.58 (2H, s), 3.73 (3H, s), 6.90 (2H, d, J = 9Hz), 7.20 (HH, d, J = 3Hz), 7.26 (2H, d, J = 9Hz), 7.32-7.38 (2H, m), 7.40 (HH, d, J = 3Hz), 7.44-7.53 (HH, m) , 7.99 (ÍH, s), 8.84 (ÍH, br s), 10.24 (ÍH, s), 10.60 (ÍH, s) MS (ESI-): 527 (MH) Example 157 (2S) -N-hydroxy-2- [5- (3- (3-methoxyphenoxy) acetylamino) phenyl) -2-thienyl 1,1-dioxide] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (110 mg) NMR (DMSO-d6, d): 1.68-2.11 (4H, m), 2.32-2.50 (H, m), 2.90 -3.66 (5H, m), 4.71 (2H, s), 6.49-6.66 (2H, m), 7.13-7.26 (2H, m), 7.31- 7.47 (2H, m), 7.52-7.72 (2H, m) , 7.94-9.14 (HH, m), 8.70 (2H, br s), 10.23 (HH, s), 10.62 (HH, s) MS (ESI-): 543 (MH) Example 158 1,1-dioxide ( 2S) -N-hydroxy-2- [5- (3- (3-phenoxypropionylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (78 mg) NMR ( DMSO-dg, d): 1.69-2.12 (4H, m), 2.35-2.50 (HH, m), 2.82 (2H, t, J = 7Hz), 2.92-3.56 (5H, m), 4.28 (2H, t , J = 7Hz), 6.95 (3H, d, J = 9Hz), 7.21 (ÍH, d, J = 3Hz), 7.29 (2H, t, J = 5Hz), 7.34-7.55 (4H, m), 8.03 ( HH, s), 8.84 (HH, s), 10.21 (HH, s), 10.60 (HH, s) MS (ESI-): 527 (MH) Example 159 (2S) -N-hydroxy 1,1-dioxide -2- [5- (3- (4-fluoro phenoxy) acetyl mino) -phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (75 mg) NMR (DMSO-d6, d): 1.69-2.11 (4H, m), 2.34-2.49 (HH, m), 2.92-3.56 (5H, m), 4.71 (2H, s), 6.97-7.36 (5H, m), 7.83-7.46 (3H, m), 7.52- 7.62 (H, S), 8.02 (H, S), 8.84 (H, S), 10.20 (H, S), 10.60 (H, S) MS (ESI-): 531 (MH Example 160 1,1-Dioxide of (2S) -N-hydroxy-2- [5- (3- (4-methoxyphenoxy) acetylamino) -phenyl) -2-thienyl] -3,4,5,6-tetrahydro -2H-thiopyran-2-acetamide (89 mg) NMR (DMS0-d6, d): 1.68-2.08 (4H, m), 2.35-2.50 (HH,), 2.94-3.30 (4H, m), 3.41-3.54 (ÍH, m), 3.70 (3H, s), 4.65 (2H, s), 6.90 (2H, d, J = 10Hz), 6.98 (2H, d, J = 10Hz), 7.21 (ÍH, d, J = 3Hz), 7.33-7.45 (3H, m), 7.54-7.62 (H, m), 8.03 (H, s), 8.84 (H, s), 10.17 (H, s), 10.60 (H, s) MS ( ESI-): 543 (MH) EXAMPLE 161 (2S) -N-Hydroxy-2- [5- (3- (2- (methylaminocarbonyloxy) -acetylamino) phenyl) -2-thienyl] -3-dioxide] , 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (68 mg) NMR (DMSO-ds, d): 1.64-2.06 (4H, m), 2.32-2.51 (H, m), 2.61 (3H , s), 2.92-3.56 (5H, m), 4.57 (2H, s), 7.12-7.54 (7H, m), 7.98 (HH, s), 10.14 (HH, s), 10.61 (HH, s) MS (ESI-): 494 (MH) Example 162 1,1-dioxide (2S) -N-hydroxy-2- (5-phenyl-2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (51 mg) NMR (DMSO-ds, d): 1.70-2.07 (4H,), 2.34-2.52 (HH, m), 2.92-3.07 (2H, m), 3.10-3.27 (2H, m), 3.30-3.50 (HH, m), 7.21 (HH, d, J = 3.5 Hz), 7.29-7.36 (HH, m), 7.43 (2H, t, J = 5Hz), 7.48 (HH, d, J = 3.5Hz), 7.65 (2H, d, J = 8Hz), 8.85 (HH, br s) MS (ESI-): 364 (MH) EXAMPLE 163 1, 1-dioxide (2S) -N-hydroxy -2 - (5- (4-ethylaminocarbonylmethoxy) -phenyl) -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (35 mg) NMR (DMSO-d6, d): 1.04 (3H, t, J = 7.2Hz), 1.71- 2.08 (4H, m), 1.35 -1.45 (HH, m), 2.95-3.50 (7H, m), 4.89 (2H, s), 7.00 (2H, d, J = 9.0Hz), 7.17 (HH, d, J = 4.0Hz), 7.35 ( HH, d, J = 4.0Hz), 7.58 (2H, d, J = 9.0Hz), 8.12 (HH, br), 8.84 (HH, s), 10.59 (HH, s) Example 164 1,1-dioxide (2S) -N-hydroxy-2- [5- (4- (methi laminocarb nor lmetoxy) -phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (450 mg) NMR (DMSO-d6, d): 1.70-2.07 (4H,), 2.35-2.45 (ÍH, m), 2.65 (3H, d, J = 4.5Hz), 2.95-3.50 (5H, m), 4.50 (2H, s), 7.01 (2H, d, J = 9.0Hz), 7.16 (HH, d, J = 4.0Hz), 7.35 (HH, d, J = 4.0Hz), 7.57 (2H, d, J = 9.0Hz), 8.06 (HH, br), 8.84 (HH, s), 10.57 (HH, s) MS (ESI-): 451 (MH) Example 165 (2S) -N-hydroxy-2- [5- (4-fluorophenyl) -2-thienyl] -2-dioxide] -2, 3 ,, 5-tetrahydrothiophen-2-acetamide (200 mg) NMR (DMSO-ds, d): 2.14-2.35 (2H, m), 2.55-2.66 (HH, m), 2.80 (HH, d, J = 15Hz) , 2.90 (HH, d, J = 15Hz), 3.05-3.40 (3H, m), 7.17 (HH, d, J = 4Hz), 7.26 (2H, d, J = 9Hz), 7.45 (HH, d, J = 4Hz), 7.70 (2H, dd, J = 5, 9Hz), 8.88 (HH, s), 10.60 (HH, s) MS (ESI-): 368 (MH) Example 166 1, 1-dioxide (2S ) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (acetoxyacetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (110 mg) was dissolved in 50% trifluoroacetic acid in dichloromethane (10 ml) and the reaction mixture was stirred at room temperature during 1 hour. Then, the mixture was concentrated in vacuo, the residue was purified by column chromatography on SiO2. (eluent: 2% MeOH in CHC13) to obtain 1,1-dioxide (2S) -N-hydroxy-2- [5- (3- (acetoxyacetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (65 mg) as a dust. NMR (DMSO-ds, d): 1.69-2.07 (4H,), 2.14 (3H, s), 2.32-2.47 (HH, m), 2.92-3.55 (5H, m), 4.67 (2H, s), 7.22 (HH, d, J = 3Hz), 7.32-7.52 (3H, m), 7.97 (HH, s) MS (ESI-): 479 (MH) Example 167 (2S) -N-hydroxy 1,1-dioxide -2- [5- (3- ((2S) -2-acetoxopropionylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetaptide (50 mg) NMR (DMSO -ds, d): 1.44 (3H, d, J = 8Hz), 1.72-2.09 (4H, m), 2.33-2.49 (ÍH, m), 2.93-3.32 (4H, m), 3.40-3.56 (ÍH, m), 5.04 (HH, q, J = 8Hz), 7.22 (HH, d, J = 3Hz), 7.32-7.53 (4H, m), 7.97 (HH, s), 8.84 (HH, s), 10.19 ( ÍH, s), 10.59 (ÍH, s) MS (ESI-): 493 (MH) Example 168 To a solution of 3-chlorophenylboronic acid (125 mg) in degassed N, N-dimethylformamide (0.5 ml) was added a suspension of tetrakis (triphenylphosphine) palladium (103 mg) in degassed N, N-dimethylformamide (2.5 ml), a 5 solution of sodium carbonate (424 mg) in degassed water (1 ml) and N- [2- (2- (5-bromo-2-thienyl) -1, l-dioxo-3, 4, 5, crowns, 6-Tetrahydro-2H-thiopyran-2-yl] acetyl] hydroxylamine trityl (59.2 μmol, 14.8 μmol / crown) ^^ under a nitrogen atmosphere.

The resultant was heated for 48 hours at 60 ° C, the crowns were washed successively with degassed N, N-dimethylformamide, a solution of sodium diethyldithiocarbamate (500 mg) and diisopropylethylamine (0.5 ml) in N, N-dimethylformamide (100 ml). ), N, N-dimethylformamide, sulfoxide 15 of methyl, water, methanol and dichloromethane. The crowns were treated with 5% trifluoroacetic acid in dichloromethane ^^ for 1 hour at room temperature and removed from the solution. Then, the solution was evaporated under a stream of nitrogen, the residue was purified by HPLC (acid 20% trifluoroacetic acid in 30% ethanol-hexanoal) to form (2S) -N-hydroxy-2- [5- (3-chlorophenyl) -2-thienyl] -3,4,5-dioxide, 6-tetrahydro-2H-thiopyran-2-acetamide (4.5 mg) as a powder. MS (ESI +): 400.2 (M + H) 5 The object compounds listed in the table were obtained from the starting compounds 1 and 2 in a manner similar to that of Example 168, according to the following reaction scheme. Reaction scheme: (Examples 169 to 190) Starting compounds 1 Table 25 The following compounds were obtained in a manner similar to that of Example 54. E 1 emplo 191 (2S) -N-hydroxy-2- [5- (3-aminoacetylamino) phenyl) 1,1-dihydrochloride - 2 - ti eni l] - 3, 4, 5, 6-tetrahydro-2H-t iopi ran-2-acetamida (3.0 g) of 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) - 2 - [5 - (3 - (2 - (t-butoxycarbonylamino) -acetylamino) f eni l) -2-tienyl] - 3, 4, 5, 6-tetrahydro-2H-t iopi ran-2-ace t ami da NMR (DMSO-d6, d): 1.68-2.10 (4H, m), 2.34-2.48 (HH, m), 2.92-3.62 (5H, m), 3.76-3.88 (2H, m), 7.23 (HH, d , J = 3Hz), 7.36-7.46 (3H, m), 7.49-7.56 (H, m), 7.99 (H, s), 10.69 (H, s), 10.92 (H, s) MS (ESI +): 438 (M + H) Example 192 1,1-Dihydroxy (2S) -Nh-idroxy-2 - [5 - (3 - (3 - (N-methylamino) -propionylamino) f-enyl) -2-thienyl] - 3, 4, 5, 6-t and rahydro-2H-t-thiopi-2-acetylamide (112 mg) of 1,1-dioxide (2 S) -N- (2-tetrahydropyranyloxy) -2- [5 - (3 - (3 - (N - t - butoxycarbonyl - N -methylamino) propionylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide NMR (DMSO-d6 , d): 1.68-2.11 (4H, m), 2.32-2.47 (ÍH, m), 2.61 (3H, t, J = 4Hz), 2.78 (2H, t, J = 7Hz), 2.90- 3.30 (6H, m), 3.38-3.62 (HH, m), 7.22 (2H, d, J = 3Hz), 7.32-7.50 (4H, m), 8.04 (HH, s), 8.36-8.58 (2H, m), 10.33 ( ÍH, s), 10.61 (ÍH, s) MS (ESI +): 466 (M + H) Example 193 1, (2 S) -N-hydroxy -2 - [5- (3- (((2 S) -2-amino-3- (3-pyridyl) propionyl) amino) phenyl) -2-thienyl-1-dioxide ] -3, 4, 5, 6 -tetr ahi dr o- 2 H- t iopi r an- 2-acet amide (250 mg) of 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) - 2 - [5 -. { 3 - ((2 S) -2- (t-butoxycarbonylamino) -3- (3-pyridyl) propionylamino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide NMR DMSO-d 6 i 1.74-2.07 4H, m, 2.36-2.46 (H, m), 2.96-3.32 (6H , m), 3.45-3.55 (HH, m), 4.24 (HH, br), 7.22 (HH, d, J = 4.0Hz), 7.39-7.48 (4H, m), 7.52-7.57 (HH, m ), 7.83-7.88 (2H, m), 8.39 (2H, br), 8.56-8.60 (2H, m), 10.57 (H, s), 10.60 (H, s) MS (ESI +): 529.1 (M + H ) E xemployment 194 (2S) -Nh-idroxy-2 - [5 - (3 - (2 - (N -methylamino) acetylamino) phenyl) -2-thienyl] -3,4-hydroxide, 5, 6 -tetrahydrate - 2 H- ti op an- 2 - acetyl (76 mg) of 1,1-dioxide (2 S) -N- (2-tetr ahi dropi r ani 1 ox i ) - 2 - [5 - (3 - (2 - (N-t-butoxycarbonylamino) -acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide NMR ( DMSO-d6, d): 1.65-2.08 (4H, m), 2.31-2.49 (HH, m), 2.63 (21H, t, J = 7Hz), 2.92-3.52 (5H, m), 3.92-4.00 (2H , m), 7.23 (HH, d, J = 3Hz), 7.34-7.45 (3H, m), 7.49-7.57 (HH, m) 7.98 (HH, s) , 8.97-9.14 (2H, m) 10.67 (HH, s), 10.94 (HH, s) MS (ESI +): 454 (M + H) Example 195 (2S) -N-hydroxy 1,1-dihydroxy chloride -2- [5- (3- (3-aminopropionylamino) phenyl) -2-ti eni I] - 3, 4, 5, 6-tetrahydro-2H-thiophenol-2 -acetamide (78 mg) of 1, 1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5 - (3 - (3 - (t-butoxycarbonylamino) -propionylamino) phenyl) -2-ti eni 1] - 3, 4, 5 , 6-tetrahydro-2H-t iop i ran-2-ace t ami da NMR (DMSO-ds, d): 1.68-2.09 (4H, m), 2.32-2.50 (ÍH, m), 2.78 (2H, d , J = 8Hz), 2.92-3.62 (7H, m), 7, 23 (ÍH, d, J = 3Hz), 7.32-7.57 (4H,), 7.92- 8.16 (4H, m), 10.45 (ÍH, s ), 10.67 (2H, s) MS (ESI +): 454 (M + H) E j. 196 1,1-Dioxide hydrochloride (2S) -Nh idroxy-2 - [5 - [3 - (((2 S) -2-amino-3-methoxypropionyl) amino) phenyl] -2-thienyl] -3,4,5,6 -tethrahydro-2H-thiopyran-2 -acet amide (1.64 g) of 1.1 - (2 S) -N- (2-tetrahydropyranyloxy) dioxide - 2 - [5 - [3 - (((2 S) -2 - (t-butoxycarboni lamino) -3-methoxypropionyl) amino) phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H -thiopyran-2-acetamide NMR (DMSO-d6, d): 1.70-2.10 (4H, m), 2.34-2.53 (HI, m), 2.94-3.06 (2H, m), 3.10-3.56 (6H, m) , 3.74-3.86 (2H, m), 4.17-4.29 (HH, m), 7.22 (HH, d, J = 3.5Hz), 7.36-7.46 (3H, m), 7.53- 7.59 (HH, m), 7.95 (HH, s), 8.30-8.44 (2H, m), 8.84 (HH, br s), 10.63 (HH, s), 10.85 (HH, br s) MS (ESI +): 482 (M + H) Example 197 1,1-dioxide (2S) -N-hydroxy-2- [5- (3- (2-hydroxyacetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2 -acetamide (58 mg) of (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2-methoxycarbonyloxyacetyl-amino) phenyl) -2-thienyl] -3-1,1-dioxide, , 5,6-tetrahydro-2H-thiopyran-2-acetamide NMR (DMSO-dg, d): 1.70-2.12 (4H, m), 2.32-2.49 (HH,), 2.91-3.28 (4H,), 3.39- 3.55 (HH, m), 4.01 (2H, d, J = 7Hz), 5.71 (HH, t, J = 7Hz), 7.22 (HH, d, J = 3Hz), 7.38-7.40 (HH, m), 1.40 (HH, d, J = 3Hz), 7.60-7.72 (HH, m), 8.08 (HH, s), 8.85 (HH, s), 9.79 (HH, s), 10.61 (HH, s) MS (ESI) -): 437 (MH) EXAMPLE 198 N-Hydroxy-2- [5- (3- (((2S) -2-hydroxypropionyl) -amino) phenyl) -2-thienyl] -3 1,1-dioxide, , 5,6-tetrahydro-2H-thiopyran-2-acetamide (65 mg) of (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (((2S)) 1,1-dioxide -2-acetoxypropionyl) amino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-t -pipethyl 2 -acet amide NMR (DMSO-d6, d): 1.33 (3H, br s), 1.67-2.12 (4H, m), 2.30-2.48 (HH, m), 2.90-3.71 (5H, m), 4.09-4.24 (HH, m), 7.21 (HH, br s), 7.38-7.48 (3H, m), 7.68-7.75 (H, m), 8.11 (H, s), 9.26 (H, s), 10.60 (H, s) MS (ESI-): 451 (MH) Example 199 A solution of 1, (2S) -N-2- (tetrahydropyranyloxy) -2- [5- (3- (3-aminopropionylamino) phenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H- dioxide thiopyran-2-acetamide (180 mg) in chloroform (5 ml) and pyridine (1 ml) was added a solution of methoxycarbonyl chloride (38.1 mg) at room temperature. After being stirred at the same temperature overnight, the mixture was concentrated in vacuo. The residue was dissolved in ethyl acetate (10 ml) and the solution was washed successively with a 5% citric acid solution, a saturated solution of sodium bicarbonate and brine, dried over magnesium sulfate, and concentrated in vacuo. . Then, the residue was dissolved in 1% hydrogen chloride in methanol (5 ml), the mixture was stirred at room temperature for 15 minutes and concentrated in vacuo. The residue was purified by column chromatography on Si02 (eluent: 2% MeOH in CHC13) to obtain (2S) -N-hydroxy-2- (5- (3- (3- (methoxycarbonylamino)) 1,1-dioxide. propionylamino) phenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopra-ran-2-acetamide (63 mg) as a powder. NMR (DMSO-d6, d): 1.22-2.11 (4H, m), 2.35-2.56 (3H, m), 2.94-3.33 (6H, m), 3.42-3.58 (H, m), 7.20 (H, d) , J = 3Hz), 7.21-7.38 (HH, m), 7.32-7.38 (2H, m), 7.40 (HH, d, J = 3Hz), 7.42-7.50 (HH, m), 8.01 (HH, s) , 8.85 (H, m) MS (ESI-): 508 (MH) Example 200 To a solution of (2S) -N- (2-tetrahydropyranyloxy) -2- (5- (4- ( t-butyloxycarbonylmethoxy) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (220 mg) in tetrahydrofuran (THF): H20 = 2: 1 (3 ml) was added lithium hydroxide monohydrate (23.9 mg) at room temperature After being stirred at the same temperature overnight, the reaction mixture was concentrated in vacuo, the resulting residue was diluted with ethyl acetate, washed with a solution of 1% citric acid and brine, dried over sodium sulfate and concentrated in vacuo to form 2- [5- (4-carboxymethoxy phenyl) -2-tetrahydropyranyloxy) -thienyl] -3, 4-dioxide. , 5, 6-tetrahydro-2H-thiopyran -2-acetamide (190 mg) as an amorphous solid. NMR (DMSO-ds, d): 1.35-1.60 (6H, m), 1.66-1.71 (2H, m), 1.73-2.05 (2H, m), 2.34-2.46 (ÍH, m), 2.90-3.50 (6H , m), 3.72-3.90 (HH, m), 4.45, 4.75 (HH, s), 4.12 (2H, s), 6.96 (2H, d, J = 9.0Hz), 7.16 (HH, d, J = 4.0 Hz), 7.32 (HH, d, J = 4.0Hz), 7.56 (2H, d, J = 9Hz) Hz), 11.2 (HH, s) MS (ESI-): 522 (MH) Example 201 To the mixture of 4- (5-oxazolyl) -benzeneboric acid cyclic ester reaction obtained in preparation 24-2) was added (2S) -N- (2-tetrahydropyranyloxy) 2- (5-bromo- 2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (679 mg), tetrakis (triphenylphosphine) palladium (0) (8.67 mg) and 2M aqueous sodium carbonate (7.5 ml) a room temperature. The mixture was stirred for 3 hours at 80 ° C and extracted between ethyl acetate and 3% aqueous sodium bicarbonate. The separated organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuo. The residue was purified by chromatography on silica gel (eluted with 0.5-3% methanol in chloroform) to form (2S) -N- (2-tetrahydropyranyloxy) -2- [5- [4- (5-oxazolyl) phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (795 mg) as an amorphous solid. NMR (CDC13, d): 1.40-1.55 (4H, m), 1.61-1.75 (2H, m), 1.91-2.02 (2H, m), 2.05-2.25 (2H, m), 2.70-2.94 (2H, m) ), 3.01-3.17 (4H, m), 3.29-3.51 (1H, m), 3.64-3.74 (ÍH,), 4.53 (0.5Hz, s), 4.82 (0.5H, s), 7.26-7.34 (2H, m), 7.39 (HH, s), 7.65 (4H, s), 7.94 (HH, s), 8.25 (0.5H, s), 8.37 (0.5H, s) MS (ESI-): 515 (MH) The following compounds were obtained in a manner similar to that of Example 89. EXAMPLE 202 (2S) -N- (2-Tetrahydropyranyloxy) -2- [5- (3-formylphenyl) -2-thienyl] -1-dioxide] - 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (0.9 g) NMR (CDC13, d): 1.40-1.75 (6H, m), 1.90-2.02 (2H, m), 2.05-2.26 ( 2H, m), 2.70-2.93 (2H, m), 3.01- 3.19 (2H, m), 3.28-3.53 (H, m), 3.62-3.75 (HH, m), 4.53, 4.83 (HH, s), 7.26-7.37 (2H, m), 7.56 (HH, dd, J = 8.0, 8.0Hz), 7.80-7.85 (2H, m) , 8.09 (OH, s), 10.05 (OH, s) MS (ESI-): 476 (MH) EXAMPLE 203 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- ( 4-ethenylphenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (2.1 g) NMR (CDCl 3, d): 1.37-1.75 (6H, m), 1.86-2.00 (2H, m), 2.05-2.25 (2H, m), 2.65-2.91 (2H, m), 3.00-3.17 (4H, m), 3.26-3.49 (HH, m), 3.59-3.70 (HH, m) , 4.51, 4.81 (ÍH, s), 5.28 (HH, d, J = llHz), 5.78 (HH, d, J = 17.7Hz), 6.66-6.75 (HH, m), 7.41 (2H, d, J = 8.0Hz), 7.55 (2H, d, J = 8.0Hz) MS (ESI-): 474 (MH) Example 204 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (2-carboxyethenyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (1.1 g) NMR (CDC13, d): 1.41-1.71 (6H, m), 1.92-2.25 (4H, m), 2.76-2.88 (2H, m), 3.05-3.19 (4H, m), 3.30-3.51 (HH,), 3.69-3.76 (HH, m), 4.54, 4.84 (ÍH, s), 6.40 (ÍH, d, J = 15Hz) , 7.45-11.74 (7H, m) MS. (ESI-): 518 (MH) EXAMPLE 205 1, 1-Dioxide (2S) -N- (5-tetrahydropyranyloxy) -2- (5-phenyl-2-thienyl) -3,, 5,6-tetrahydro- 2H-thiopyran-2-acetamide (93 mg) NMR (CDCl3, d): 1.39-1.75 (6H, m), 1.90-2.00 (2H, m), 2.04-2.24 (2H, m), 2.63-2.91 (2H , m), 3.03-3.18 (4H, m), 3.27-3.50 (HH, m), 3.59-3.70 (HH, m), 4.53 (0.5H, s), 4.80 (0.5H, s), 7.24-7.41 (5H,), 7.56-7.63 (2H, m), 7.95 (0.5H, s), 8.12 (0.5H, s) MS (ESI-): 448 (MH) Example 206 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (t-but i lox i carboni lme toxi) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran- 2-acetamide (3.8 g) NMR (DMS0-d6, d): 1.35-1.60 (15H, m), 1.65-1.71 (2H, m), 1.73-2.04 (2H, m), 2.34-2.45 (H, m) ), 2.90-3.50 (6H,), 3.72-3.90 (ÍH, m), 4.45, 4.75 (ÍH, s), 4.73 (2H, s), 7.01 (2H, d, J = 9.0Hz), 7.15 (ÍH) , 2 d, J = 4.0Hz), 7.33 (ΔH, d, J = 4.0Hz), 7.55 (2H, d, J = 9.0Hz) Example 207 (2S) -N- 1,1-dioxide was obtained ( 2-tetrahydropyranyloxy) -2- [5- (4- (ethylaminocarbonylmethoxy) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (65 mg) in a manner similar to that of Example 201. NMR (DMSO-ds, d) : 1.04 (3H, t, J = 7.2Hz), 1.37- 1.63 (6H, m), 1.69-1.81 (2H, m), 1.83-2.04 (2H, m), 2.35-2.47 (ÍH,), 2.67- 3.51 (5H,), 3.74-3.90 (HH, m), 3.95, 4.75 (HH, s), 4.49 (2H, s), 7.00 (2H, d, J = 9.0Hz), 7.15-7.20 (HH, m ), 7.33-7.36 (HH, m), 7.58 (2H, d, J = 9.0Hz), 8.13 (HH, br) Example 208 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2 - [5- (3- (propylamino car bon i lamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (140 mg) NMR (DMSO-ds, d): 0.88 (3 H, t, J = lHz), 1.26- 2.09 (12H, m), 2.43-2.46 (HH, m), 2.76-3.56 (6H, m), 3.72-3.92 (HH, m) , 4.44, 4.75 (ÍH, s), 6.11-6.24 (ÍH, m), 7.09-7.42 (6H, m), 7.85 (ÍH, s) (ÍH, s) MS (ESI-): 548 (MH) following compounds were obtained in a manner similar to that of Example 129. Example 209 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (isopropylaminocarbonylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (160 mg) NMR (DMSO-) ds, d): 1.10 (6H, m), 1.30-2.10 (10H, m), 2.34-2.47 (HH, m), 2.83-3.30 (5H, m), 3.40-3.53 (1H, m), 3.18- 3.90 (2H, m), 4.36, 4.44 (H, s), 6.04 (H, d, J = 8Hz), 7.09-7.40 (6H, m), 7.85 (H, s), 8.44 (H, s) MS (ESI-): 548 (MH) EXAMPLE 210 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2-chloroethylaminocarbonamino) phenyl] -2-thienyl 1,1-dioxide ] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (335 mg) NMR (CDC13, d): 1.46 (2H, br), 1.62-1.67 (4H, m), 1.84-1.96 ( 2H, m), 2.74-2.88 (2H, m), 2.96-3.06 (1H, m), 3.08-3.14 (2H, m), 3.31- 3.41 (2H, m), 3.49-3.54 (ÍH, m), 3.55-3.60 (2H, m), 3.66 (2H, t, J = 6.0Hz), 3.70-3.80 (ÍH, m), 4.48 (1 / 2H, br), 4.84 (172H, br), 7.17-7.24 ( 4H,), 7.30-7.50 (5H, m) MS (ESI-): 568.4 (MH) Example 211 To a solution of (2S) -N- (2-tetrahydropyranyloxy) 1,1-dioxide i) -2- [5- (3-amino phenyl) -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (7.00 g), ethoxyacetic acid (2.04 g) and 1-hydroxybenzotriazole (2.65 g) in N, N-dimethylformamide (80 ml) was added hydrochloride of 1 ethyl-3- (3-dimethylaminopropyl) carbodiimide (WSCD HCl) (3.75 g) at room temperature. After being stirred at the same temperature overnight, the mixture was concentrated in vacuo. The residue was dissolved in ethyl acetate (200 ml) and the solution was washed successively with a 5% citric acid solution, a saturated aqueous solution of sodium bicarbonate and brine, dried over magnesium sulfate, and concentrated to a empty. The residue was purified by Si02 column chromatography (eluent 1% MeOH in CHC13) to obtain (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2-ethoxyacetylamino) 1,1-dioxide. ) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (7.00 g). NMR (DMSO-d6, d): 1.20 (3H, t, J = 7Hz), 1.33-1.62 (6H, m), 1.70-2.12 (4H, m), 2.35-2.50 (ÍH, m), 2.88-3.22 (5H, m), 3.38-3.52 (2H, m), 3.58 (2H, q, J = 7Hz), 3.75-3.92 (ÍH, m), 4.44, 4.75 (ÍH, s), 7.18-7.25 (ÍH, m), 7.34-7.45 (3H, m), 7.55-7.64 (HH, m), 8.03 (HH, s), 9.81 (HH, s), 11.24 (HH, s) MS (ESI-): 549 (MH ) The following compounds were obtained in substantially the same manner as that of Example 211. EXAMPLE 212 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- (methylaminocarbonyloxy) dioxide ) acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (144 mg) NMR (DMSO-ds, d): 1.36-2.10 (10H, m), 2.36-2.51 (ÍH, m), 2.60 (3H, d, J = 6Hz), 2.87-3.30 (5H, m), 3.40-3.54 (ÍH, m), 3.72-3.90 (ÍH, m), 4.43, 4.76 (ÍH, m), 4.57 (2H, s), 7.18-7.30 (2H, m), 7.35-7.52 (4H, m), 7.99 (ÍH, s), 10.14 (ÍH, s), 11.25 (ÍH, s ) MS (ESI-): 578 (MH) EXAMPLE 213 1 (1S-Dioxide) (2S) -N- (2-tetrahydropyranyloxy) -2- [ 5- (3- ((2S) -2- (tert-butoxycarbonylamino) -3-methoxypropionyl-amino) phenyl] -2-thienyl] -3,, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (2.90 g) NMR (CDC13, d): 1.37-1.51 (11H, m), 1.59-2.01 (6H, m), 2.04-2.25 (2H, m), 1.64-2.91 (2H, m), 3.00-3.17 (4H ,), 3.26-3.50 (4H, m), 3.53-3.72 (2H, m), 3.80-3.94 (HH, m), 4.34-4.45 (HH, m), 4.53 (0.5H, s), 4.82 (0.5 H, s), 5.45-5.59 (HH, m), 7.20-7.36 (5H, m), 7.43-7.51 (1H, m), 7.75-7.83 (HH, m), 8.18 (0.5H, s), 8.31 (0.5H, s), 8.49 (H, br s) MS (ESI +): 683 (M + H + NH 3) Example 214 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [ 5- (3- (2- (4-methoxy phenyl) acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (160 mg) NMR (CDC13, d ): 1.36-1.76 (8H, m), 1.86-1.98 (2H, m), 2.04-2.22 (2H, m), 2.69-2.92 (2H,), 3.02-3.17 (2H, m), 3.26-3.51 ( ÍH,), 3.62-3.73 (ÍH, m) -, 3.68 (2H, s), 3.82 (3H, s), 4.52, 4.72 (ÍH, s), 6.87-6.95 (2H, m), 7.13-7.32 ( 6H, m), 7.45-7.56 (3H, m), 8 .56, 8.59 (OH, s) MS (ESI-): 611 (MH) EXAMPLE 215 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- (te r-bu toxy carboni lamino) acetyl) amino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (246 mg) NMR (DMSO-d6, d) : 1.26-1.63 (6H, m), 1.40 (9H, s), 1.68-2.06 (4H, m), 2.35-2.48 (ÍH, m), 2.88-3.30 (5H, m), 3.36-3.53 (ÍH, m), 3.74 (2H, d, J = 7Hz), 3.72-3.92 (HH, m), 4.43, 4.75 (HH, s), 7.03-7.12 (HH, m), 7.18-7.24 (HH, m), 7.40-7.53 (4H, m), 7.98 (HH, s), 10.05 (HH, s), 11.25 (HH, s) MS (ESI-): 620 (MH) Example 216 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3 -propoxyacetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (3.68 g) NMR ( CDC13, d): 1.01 (3H, t, J = 7Hz), 1.36-1.78 (10H, m), 1.88-1.99 (2H, m), 2.03-2.25 (2H, m), 2.65-2.93 (2H, m ), 2.98-3.18 (2H, m), 3.28-3.52 (HH, m), 3.58 (2H, t, J = 7Hz), 3.62-3.74 (HH, m), 4.07 (2H, s), 4.52, 4.82 (ÍH, s), 7 .23-7.38 (4H, m), 7.52-7.59 (H, m), 7.80 (H, s), 8.19, 8.32 (H, s), 8.56 (H, s) MS (ESI-): 563 (MH Example 217 1, 1-Dioxide of (2S) -N- (2-tetrahydropyranyloxy) -2- [5-. { 3- (n-2 -but i lox i acet i lamino) phenyl} -2-tienil] -3, 4, 5, 6-tetrahydro-2-H-thiopyran-2-acetamide (140 mg) NMR (CDCI3, d): 1.95 (2H, br), 2.08-2.23 (2H, m), 2.64-2.88 (2H , m) 3.06 (2H, s), 3.16 (2H, br), 3.39-3.50 (2H, m) 3.62 (2H, t, J = 7.5Hz), 4.06 (2H, s), 4.54 (1 / 2H, br), 4.80 (1 / 2H, br), 7.21-7.30 (2H,), 7.34-7.36 (2H, m), 7.52-7.56 (HH, m), 7.80 (HH, s), 7.94 (1 / 2H , s), 8.12 (1 / 2H, s), 8.34 (OH, s) MS (ESI-): 577.3 (MH) Example 218 1.1-(2S) -N- (2-tetrahydropyranyloxy) -2 dioxide - [5- (3- (3-me tox i rop i oni lamino) phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (4.34 g) NMR (CDC13 , d): 1.46 (2H, br), 1.57-1.70 (2H, m), 1.95 (2H, t, J = 6.0Hz), 2.07-2.20 (2H, m), 2.66 (2H, t, J = 6.0 Hz), 2.70-2.89 (2H, m), 3.06 (2H, s), 3.10-3.16 (2H, m), 3.26- 3.44 (HI, m), 3.47 (3H, s), 3.62-3.10 (2H, m), 3.75 (2H, t, J = 6.0Hz), 4.52 (1 / 2H, br), 4.82 (1 / 2H, br), 7.20-7.25 (2H, m), 7.28-7.31 (2H, m) , 7.46-7.51 (ÍH, m), 7.70-7.73 (ÍH, m), 8.18 (1 / 2H, s), 8.31 (1 / 2H, s ), 8.31 (OH, s) MS (ESI-): 549.4 (MH) EXAMPLE 219 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (methoxyacetylamino) phenyl) 1,1-dioxide } -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (3.24 g) NMR (CDCl 3, d): 1.46 (4H, br), 1.55-1.58 (2H, m), 1.94 (2H, br), 2.07-2.20 (2H, m), 2.66- 2.88 (2H, m), 3.05 (2H, s), 3.09-3.14 (2H, m), 3.27-3.48 (ÍH, m), 3.53 (3H, s), 3.60- 3.72 (HH, m), 4.04 (2H, s), 4.52 (1 / 2H, br), 4.81 (1 / 2H, br), 7.23-7.30 (2H, m), 7.43- 7.46 (2H, m), 7.55-7.59 (HH, m), 7.80 (HH, s), 8.04 (1 / 2H, s), 8.20 (1 / 2H, s), 8.30 (HH, s) MS (ESI-): 535.3 (MH) EXAMPLE 220 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (3- (9-f luorenylmethoxycarbonylamino) propionylamino) phenyl) -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (2.70 g) NMR (CDCI3, d): 1.31-1.81 (5H, m), 1.84-2.28 (4H,) , 2.58-2.76 (2H, m), 2.92-3.22 (4H, m), 3.30-3.84 (4H, m), 4.02-4.22 (2H, m), 4.37-4.49 (1H, m), 4.62, 4.94 ( ÍH, s), 6.89-7.90 (13H, m), 7.99-8.14 (2H, m), 8.66, 10.00, 10.46 (HH, s) MS (ESI-): 756 (MH) Example 221 1, 1-dioxide of (2S) -N- ( 2-tetrahydropyranyloxy) -2- [5- (3-phenoxyacetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (4.90 g) NMR (CDC13, d) : 1.37-1.76 (8H, m), 1.88-1.99 (2H, m), 2.05-2.26 (2H, m), 2.67-2.92 (2H, m), 2.98- 3.18 (2H, m), 3.28-3.51 ( ÍH, m), 3.6.2-3.75 (ÍH, m), 4.62 (2H, s), 4.52, 4.82 (ÍH, s), 6.96-7.11 (3H, m), 7.23-7.30 (2H, m), 7.32-7.40 (4H, m), 7.58-7.62 (HH, m), 7.79 (HH, s), 8.24, 8.35 (HH, s), 8.36 (HH, s) MS (ESI-): 597 (MH) EXAMPLE 222 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- (3-methoxy-enoxy) -acetylamino) -phenyl) -2-thienyl] -3,4-dioxide , 5,6-tetrahydro-2H-thiopyran-2-acetamide (140 mg) NMR (DMSO-d6, d): 1.34-1.77 (8H, m), 1.86-1.99 (2H, m), 2.05-2.24 (2H , m), 2.66-2.90 (2H, m), 3.03-3.17 (2H, m), 3.28-3.52 (HH, m), 3.62-3.74 (HH, m), 3.82 (3H, s), 4.52, 4.82 (ÍH, s), 4.61 (2H, s), 6.52-6.65 (3H, m), 7.22-7.30 (3H, m), 7.33-7.42, (2H, m), 7.55- 7.62 (HH,), 7.72 -7.82 (ÍH, m), 8.26-8.42 (2H, m) MS (ESI-): 627 (MH) EXAMPLE 223 1 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (3-phenoxypropionyl amino) phenyl) -2-dioxide) -2 -thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (135 mg) NMR (CDCl 3, 6): 1.32-1.78 (8H, m), 1.86-1.96 (2H, m), 2.06-2.25 (2H, m), 2.71-2.92 (2H, m), 2.86 (2H, t, J = 7Hz), 3.01-3.20 (2H, m), 3.28-3.52 (ÍH, m), 3.63-3.77 (HH, m), 4.35 (2H, t, J = 7Hz), 4.54, 4.84 (HH, s), 6.78-7.03 (4H, m), 7.12-7.36 (5H, m), 7.47-7.65 (2H, m), 8.13 (HH, s), 8.73 (HH, s) MS (ESI-): 644 (MH) Example 224 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5 - (3- (2- (4-fluorophenoxy) acetylamino) phenyl) -2-thienyl] -3, 4,5,6-tetrahydro-2H-thiopyran-2-acetamide (158 mg) NMR (CDCl 3, d): 1.35-2.01 (10H, m), 2.05-2.23 (2H, m), 2.66-2.94 (2H, m), 3.01-3.19 (2H, m), 3.29-3.53 (ÍH,), 3.62-3.26 (ÍH, m), 4.53, 4.82 (ÍH, s), 4.58 (2H, s), 6.92-7.10 (5H, m), 7.24-7.39 (3H,), 7.56-7.62 (IH, m), 7.73-7.77 (IH, m), 8.34 (IH, s), 8.39, 8.49 (IH, s) MS (ESI-) : 615 (MH) EXAMPLE 225 ((2S) -N- (2-Tetrahydropyranyloxy) -2- [5- (3- (2- (4-methyl-phenoxy) -acetylamino) phenyl) 1,1-dioxide - 2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (150 mg) NMR (CDCl 3, d): 1.36-1.78 (8H, m), 1.87-2.01 (2H, m) , 2.06-2.26 (2H, m), 2.65-2.94 (2H, m), 3.02-3.23 (2H, m), 3.27-3.56 (HH, m), 3.62-3.36 (HH, m), 3.80 (3H, s), 4.52, 4.83 (ÍH, s), 4.57 (2H, s), 6.84-7.03 (4H, m), 7.24-7.43 (4H, m), 7.54-7.67 (ÍH, m), 7.80 (ÍH, s), 8.28-8.49 (2H, m) MS (ESI-): 627 (MH) Example 226 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- ( 3- (N-tert-butoxycarbonyl-N-methylamino) propionylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (160 mg) NMR (CDCl 3, d) : 1.38-1.75 (8H,), 1.48 (9H, s), 1.88-2.01 (2H, m), 2.06-2.24 (2H, m) 2.62- 2.88 (4H, m), 2.91 (3H, s), 3.02 -3.17 (2H, m ), 3.27-3.50 (HH, m), 3.58-3.75 (3H, m), 4.53, 4.32 (HH, s), 7.18-7.31 (6H, m), 7.52-7.59 (HH, m), 7.70-7.83 (1H, m) MS (ESI-): 648 (MH) EXAMPLE 227 1 (2S) -N- (2-tetrahydropyranyloxy) -2- [5-. { 3- ((2S) -2- (tert-butoxycarbonyl amino) -3- (3-pyridyl) propionylamino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (1.54 g) NMR (DMSO-d6, d): 1.22-1.21 (2H, m), 1.43 (9H, s ), 1.63-1.68 (4H, m), 1.98 (2H, br), 2.07-2.25 (2H, m), 2.74-2.98 (2H, m), 3.04-3.20 (6H, m), 3.41- 3.48 (H) , m), 3.66-3.76 (ÍH, m), 4.45 (1 / 2H, br), 4.54-4.63 (ÍH, br), 4.86 (1 / 2H, br), 5.31- 5.45 (1H, m), 6.82 -7.00 (2H, m), 7.04-7.20 (3H,), 7.22-7.27 (2H, m), 7.52-7.65 (2H, m), 8.43- 8.59 (3H, m) MS (ESI +): 713.1 (M + H) Example 228 (2S) -N- (2-tetrahydropyranyloxy-2- (5- [3- [2- (2-propenyl-yloxy) acetyl] aminophenyl] -2-thienyl 1,1-dioxide ] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (14.6 g) NMR (CDC13, d): 1.37-1.76 (6H, m), 1.88-2.01 (2H, m), 2.04- 2.26 (2H, m), 2.64-2.92 (2H, m), 3.00-3.17 (4H, m), 3.27-3.51 (HH, m), 3.61-3.72 (HH, m), 4.08 (2H, s), 4.16 (2H, d, J = 6Hz), 4.52 (0.5H, s), 4.81 (0.5H, s), 5.33 (HH, d, J = 9Hz), 5.37 (HH, d, J = 16.5Hz), 5.90-6.04 (ÍH, m), 7.23-7.39 (5H, m), 7.53- 7.60 (ÍH,), 7.80 ( H, s), 8.16 (0.5H, s), 8.22 (0.5H, s), 8.35 (H, s) MS (ESI-): 561 (MH) Example 229 1, 1-dioxide (2S) -N - (2-tetrahydropyranyloxy) -2- [5- (3- (2- (ethoxycarbonylamino) acetylamino) phenyl] -2-thiyl enyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide ( 4 g) NMR (CDC13, d): 1.28 (3H, t, J = 7.5Hz), 1.41 (2H, br), 1.92 (2H, br), 2.04-2.17 (2H, m), 2.55 (4H, br ), 2.73-2.91 (2H, m), 3.02-3.13 (4H, m), 3.28-3.49 (HH, m), 3.64-3.74 (HH, m), 4.03-4.05 (2H, m), 4.20 (2H) , q, J = 7.5Hz), 4.52 (1 / 2H, br), 4.83 (1 / 2H, br), 7.11- 7.21 (3H, m), 7.37-7.43 (HI, m), 7.48-7.56 (2H , m), 7.74-7.80 (HH, m), 8.46 (HH, br) MS (ESI-): 628.2 (M-H + Cl) Example 230 1, 1-dioxide (2S) -N- (2- tetrahydropyranyloxy) -2- [5- (3- (2- (N- tert -butoxycarboni 1-N-methylamino) acetylamino) phenyl) -2-thiyl enyl] -3,4,5,6-tetrahydro-2H- t iopi ran-2 -acet amide (119 mg) NMR (CDCl 3, d): 1.35-2.74 (8H, m), 1.51 (9H, s), 1.88-2.00 (2H, m), 2.05-2.55 (2H, m), 2.18-2.92 (2H , m), 3.03 (3H, s), 3.05-3.16 (2H, m), 3.28-3.50 (HH, m), 3.62-3.76 (HH, m), 3.99 (2H, s), 4.53, 4.83 (HH) , s), 7.22-7.34 (4H, m), 7.43 (HH, brs), 7.67-7.85 (HH, m), 8.42, 8.50 (HH, s) MS (ESI-): 634 (MH) Example 231 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (3- (tert-butoxycarbonylamino) propionylamino) phenyl) -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (150 mg) NMR (CDC13, d): 1.35-1.72 (8H, m), 1.44 (9H, s), 1.88-2.01 (2H, m), 2.05-2 , 23 (2H, m), 2.57- 2.67 (2H, m), 2.75-2.89 (2H, m), 3.00-3.17 (4H, m), 3.28-3.56 (3H, m), 3.65-3.76 ( ÍH, m), 4.54, 4.84 (ÍH, s), 5.28 (ÍH, br s), 7.13-7.28 (4H, m), 7.48-7.66 (2H, m), 8.14 (ÍH, br s), 8.75, 8.78 (OH, s) MS (ESI-): 634 (MH) The following compounds were obtained in a manner similar to that of Example 130. EXAMPLE 232 1.1-Dioxide (2 S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (propionylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (160 mg ) NMR (DMSO-d6, d): 1.09 (3H, t, J = 7Hz), 1.32-2.07 (10H, m), 2.36 (2H, q, J = 7Hz), 2.37-2.47 (ÍH, m), 11.88-3.22 (5H, m), 3.35-3.54- (ÍH, m), 3.74-3.92 (ÍH, m), 4.44, 4.75 (ÍH, s), 7.17-7.25 (ÍH, m), 7.30-7.42 ( 3H, m), 7.43-7.52 (HH,), 8.00 (HH, s), 9.98 (HH, s), 11.36 (HH, s) MS (ESI-): 519 (MH) Example 233 1, 1 - (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (butyrylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-dioxide acetamide (166 mg) NMR (CDC13, d): 1.01 (3H, t, J = 7Hz), 1.35-1.84 (10H, m), 2.05-2.25 (2H, m), 2.37 (2H, t, J = 7Hz ), 2.66-2.92 (2H, m), 2.97-3.17 (2H, m), 3.27-3.52 (HH, m), 3.60-3.77 (HH, m), 4.54, 4.74 (HH, s), 7.08-7.32 (5H, m), 7.48- 7.66 (2H,), 8.64 (HH, br) MS (ESI-): 533 (MH) Example 234 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) - 2- [5- (3- (2- toxietoxycarbonyl amino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2-H-thiopyran-2-acetamide (120 mg) NMR (CDCl 3, d): 1.37-1.78 (8H, m), 1.89-2.00 (2H, m), 2.05-2.25 (2H, m), 2.67-2.94 (2H, m), 3.02-3.18 (3H, m), 3.26-3.52 (HI, m), 3.58-3.69 (2H) , m), 3.66 (3H, s), 4.25-4.32 (2H, m), 4.52, 4.83 (H, s), 6.90-7.00 (H, m), 7.20-7.32 (5H, m), - 7.63 ( ÍH, s), 8.34, 8.46 (HH, s) MS (ESI-): 565 (MH) Example 235 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3 - (2- (9-f luorenylmethoxy carboni lamino) acetylamino) phenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (486 mg) NMR (DMSO-d6, d ): 1.34-1.62 (6H, m), 1.71-2.08 (4H, m), 2.36-2.47 (ÍH, m), 2.88-3.34 (5H, m), 3.39-3.52 (2H, m), 3.74-3.92 (3H, m), 4.19-4.37 (3H, m), 4.42, 4.77 (H, s), 7.18- 7.27 (2H, m), 7.32-7.52 (7H, m), 7.62-7.70 (H, m) , 7.75 (2H, d, J = 7Hz), 7.92 (2H, d, J = 7Hm), 8.02 (H, s) Example 236 1, 1-dioxide (2S) -? - (2-tetrahydropyranyloxy) -2 - [ 5- (3- (acetoxyacetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (260 mg)? MR (CDC13, d): 1.35-1.77 (8H , m), 1.86-2.00 (2H, m), 2.03-2.24 (2H,), 2.71-2.92 (2H, m), 3.00-3.20 (2H, m), 3.38-3.54 (ÍH, m), 3.65- 3.78 (HH, m), 4.52, 4.72 (HH, s), 4.72 (2H, s), 7.14-7.35 (4H, m), 7.52, 7.59 (HH, s), 7.56-7.67 (HH, m), 8.06-8.15 (HH, m), 8.59-6.70 (HH, m) MS (ESI-): 563 (MH) Example 237 1, 1-dioxide (2S) -? - (2-tetrahydropyranyloxy) -2- [ 5- (3- ((2S) -2-acetoxypropionylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (313 mg) NMR (CDCl 3, d): 1.38-1.78 (8H, m), 1.49, 1.57 (3H, d, J = 8Hz), 1.88-2.00 (2H, m), 2.07-2.22 (2H, m), 2.72-2.92 (2H, m), 3.03 -3.19 (2H, m), 3.29-3.56 (HH, m), 3.64-3.78 (HH, m), 4.53, 4.82 (HH, s), 5.06, 5.34 (HH, q, J = 8Hz), 7.18-7.36 (4H, m), 7.53-7.68 (2H, m), 8.10 (OH, br s), 8.55, 8.59 (2H, s) MS (ESI-): 577 (MH) Example 238 1, 1- (2S) -N- (2-) dioxide tetrahydropyranyloxy) -2- [5- (3- (chloroacetylamino) phenyl] -2-thienyl] -3,,, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (201 mg) NMR (CDCI3, d): 1.40-1.54 (4H, m), 1.60-1.73 (2H, m), 1.88-2.00 (2H, m), 2.06-2.25 (2H, m), 2.67-2.91 (2H, m), 3.02-3.18 (4H, m), 3.29-3.51 (ÍH, m), 3.62-3.75 (ÍH, m), 4.21 ( 2H, s), 4.53 (0.5H, s), 4.92 (0.5H, s), 7.23-7.29 (2H, m), 7.32-7.41 (2H, m), 7.51- 7.59 (H, m), 7.70- 7.76 (1H, m), 8.22 (0.5H, s), 8.28-8.36 (1.5H, s) MS (ESI-): 539 (MH) Example 239 (2S) -N- (2) 1,1-dioxide -tetrahydropyranyloxy) -2- [5- (3- (2- (9- (f-luorenylmethoxycarbonylamino) -acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide ( 478 mg) was dissolved in a solution of 20% piperidine in N, N-dimethylformamide (8 ml) at room temperature After being stirred at the same temperature for 1 hour, the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography on Si02 (eluent: 1.5% MeOH in CHC13) to form (2S) -N- (2-tetrahydroxy-2-dioxide) idropyranyloxy) -2- [5- (3- (2-aminoacetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (335 mg) NMR (DMSO- ds, d): 1.37-1.65 (6H, m), 1.70-2.08 (4H, m), 2.34-2.50 (HH, m), 2.87-3.52 (8H, m), 3.72-3.90 (HH, m), 4.44, 4.75 (ÍH, s), 7.18-7.25 (ÍH, m), 7.32-7.44 (3H, m), 7.52- 7.60 (ÍH,), 8.02 (ÍH, s) MS (ESI +): 522 (M + H) Example 240 1,1-Dioxide of (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (3-aminopropionylamino) phenyl) -2-thienyl] -3,4,5 was obtained , 6-tetrahydro-2H-thiopyran-2-acetamide (1.56 g) in a manner similar to that of Example 239. NMR (DMSO-d6, d): 1.32-2.09 (10H, m), 1.32-2.48 (3H, m), 2.72-3.56 (8H, m), 3.72-3.90 (HH, m), 4.45, 4.75 (HH, s), 7.17-7.24 (HH, m), 7.28-7.51 (3H, m), 7.43- 7.54 (HH, m), 8.01 (HH, s), 12.4 (HH, brs) MS (ESI-): 534 (MH) Example 241 (2S) -N- (2-1-) dioxide was obtained tetrahydropyranyloxy) -2- [5- (3- (2- (methoxycarbonylamino) acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2 H-thiopyran-2-acetamide (88 mg) in a manner similar to that of Example 130. NMR (CDC13, d): 1.36-1.72 (5H, m), 1.87-1.99 (2H, m), 2.07-2.27 ( 2H, m), 2.79-2.92 (2H, m), 3.00-3.23 (2H,), 3.28-3.52 (HH, m), 3.68-3.76 (HH, m), 3.75 (3H, s), 3.96-4.12 (2H, m), 4.53, 4.94 (HH, s), 5.76-5.68 (HH, m), 7.05-7.22 (5H, m), 7.36-7.55 (2H, m), 8.40 (HH, s) MS ( ESI-): 578 (MH) Example 242 To a solution of (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3-formylphenyl) -2-thienyl 1,1-dioxide] -3 , 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (100 mg) in tetrahydrofuran (1.5 ml) was added dropwise sodium borohydride (8.71 mg) in water (0.7 ml) at room temperature. After being stirred for 30 minutes, the reaction was stopped by adding an aqueous solution of citric acid at 1%. The reaction mixture was extracted with ethyl acetate and the solution was washed with brine, dried over MgSO4 and concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel (eluent: 0.5, 3% methanol in chloroform) to form (2 S) -N- (2-tetrahydropyranyloxy) -2- [5] dioxide. - (3-hydroxymethylphenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (96 mg) as an amorphous solid. NMR (CDC13, d): 1.38-1.72 (6H, m), 1.81-2.00 (2H, m) 2.03-2.25 (2H, m), 2.67-3.17 (6H, m), 3.29-3.51 (ÍH, m) , 3.61-3.72 (HH, m), 4.52, 4.81 (HH, s), 4.72 (2H, d, J = 6.0Hz), 7.25-7.41 (4H, m), 7.52 (HH, d, J = 8.5Hz ), 7.60 (OH, s) MS (ESI-): 478 (MH) EXAMPLE 243 A solution of (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4-ethenyl) 1,1-dioxide phenyl) -2-thiyl enyl] - 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (200 mg), microencapsulated osmium tetraoxide (5.34 mg) and N-oxide N-methylmorphine (98.5 mg) in a mixture of H20-acetone-acetonitrile (1: 1: 1) (3.0 ml) was stirred at room temperature for 12 hours. After the reaction was complete, the catalyst was removed by filtration. After washing with methanol, the combined filtrates were concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel (eluent: 0.5-3% methanol in chloroform) to form 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- ( 4- (cis-1, 2-dihydroxyethyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide as an amorphous solid (200 mg). NMR (CDC13, d): 1.38-1.75 (6H, m), 1.90-2.00 (2H, m), 2.07-2.23 (2H, m), 2.00-2.89 (2H, m), 3.09-3.17 (4H, m) ), 3.25-3.50 (HH, m), 3.59-3.71 (1H, m), 3.73-3.82 (HH, m), 4.52, 4.80 (1H, 3), 4.80-4.88 (HH, m), 7.34 -7.40 (3H, m), 7.54-1.59 (3H, m) MS (ESI-): 508 (MH) Example 244 (2S) -N- (2-tetrahydropyranyloxy) -2-dioxide was obtained [5- (3- (f-enoxycarbonyloxymethyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (620 mg) of (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3-hydroxymethylphenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H 1,1-dioxide thiopyran-2-acetamide (500 mg) in a manner similar to that of Example 130. NMR (CDCl 3, d): 1.38-1.75 (6H, m), 1.90-2.01 (2H, m), 2.06-2.23 (2H , m), 2.65-2.90 (2H, m), 3.04-3.17 (4H,), 3.30-3.50 (HH, m), 3.62-3.70 (1H, m), 4.53, 4.81 (HH, s), 5.28 (2H, s), 7.19 (22H, d, J = 8-5Hz), 7.25-1.31 (4H, m), 7.37-7.42 (4H, m), 7.59-7.61 (HH, m), 7.66 (HH) , s) MS (ESI-): 598 (MH) EXAMPLE 245 To a solution of (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (phenoxycarbonyloxymethyl) phenyl) 1,1-dioxide) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (200 mg) in N, N-dimethylformamide (3 ml) was added 40% aqueous methylamine (0.17 ml). After being stirred for 3 hours at the same temperature, the mixture was concentrated in vacuo. The residue was diluted with ethyl acetate, washed with an aqueous solution of citric acid 1%, a saturated solution of NaHCO 3 and brine, dried over MgSO 4 and concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel (eluent: CHC13) to form (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (methylaminocarbonyloxy-methyl) 1,1-dioxide ) phenyl) -2-thienyl] -3,, 5,6-tetrahydro-2H-thiopyran-2-acetamide (150 mg) as an amorphous solid. NMR (CDC13, d): 1.37-1.75 (6H, m), 1.90-2.00 (2H, m), 2.05-2.23 (2H, m), 2.83 (3H, d, J = 5.0Hz), 2.89-3.17 ( 6H, m), 3.29-3.50 (HH, m), 3.61-3.71 (HH, m), 4.53-4.81 (HH, s), 5.11 (2H, s), 7.25-7.31 (2H, m), 7.36 ( ÍH, dd, J = 8.0, 8.0Hz), 7.51-7.59 (3H, m) MS (ESI-): 535 (MH) Example 246 (2S) -N- (2-tetrahydropyranyloxy) 1,1-dioxide was obtained ) -2- [5- (4- (2- (methylaminocarbonyl) ethenyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (270 mg) of 1 , 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (2-carboxyethenyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran -2-acetamide (300 mg) in a manner similar to that of Example 32. NMR (CDC13, d): 1.38-1.73 (6H, m), 1.88-2.02 (2H, m), 2.09-2.25 (2H, m ), 2.78-2.99 (2H, m), 2.96 (3H, d, J = 5Hz), 3.05-3.19 (4H, m), 3.29-3.51 (HH, m), 3.65-3.75 (HH, m), 4.54 , 4.84 (HH, s), 6.40 (HH, d, J = 15Hz), 7.20- 7.59 (7H, m), 8.78 (HH, d, J = 5Hz) Example 247 1, 1-dioxide (2S) - N- (2-tetrahydr) opyranyloxy) -2- [5- (4- (2- (ethylaminocarbonyl) ethenyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (280 mg) was obtained in a manner similar to that of Example 32. NMR (DMSO-d6, d): 1.23 (3H, t, J = 7.2Hz), 1.38- 1.73 (6H, m), 1.90-2.01 (2H, m), 2.07 -2.23 (2H, m), 2.78-2.88 (2H, m), 3.02-3.20 (4H, m), 3.38-3.48 (3H, m), 3.67-3.76 (H, m), 4.54, 4.84 (H, s), 6.41 (HH, d, J = 15Hz), 7.21-7.59 (7H, m), 8.78 (HH, br) Example 248 (2S) -N- (2-tetrahydropyranyloxy) 1,1-dioxide was obtained -2- (5- (4- (methylaminocarbonylmethoxy) phenyl) -2-thienyl] -3,, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (720 mg) in a manner similar to that of Example 247 NMR (DMSO-ds, d): 1.37-1.62 (6H, m), 1.67-1.81 ( 2H,), 1.82-2.05 (2H, m), 2.33-2.45 (ÍH, m), 2.66 (3H, d, J = 4.5Hz), 2.90-3.50 (6H, m), 3.73-3.91 (ÍH, m ), 4.45, 4.75 (HH, s), 4.50 (2H, s), 7.01 (2H, d, J = 9.0Hz), 7.16 (HH, d, J = 4.0Hz), 7.32 (HH, d, J = 4.0Hz), 7.59 (2H, d, J = 9.0Hz), 8.07 (HH, br), 11.23 (HH, s) Example 249 A mixture of (2S) -N- (2-tetrahydropyranyloxy) 1,1-dioxide ) -2- [5- [3- (Chloroacetylamino) phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (98 mg), n-tetrabutylammonium iodide (5) mg) and 2-aminoethanol (27.7 mg) in N, N-dimethylformamide (1.5 ml) was stirred for 14 hours at room temperature. The mixture was concentrated in vacuo and extracted between ethyl acetate and saturated aqueous sodium bicarbonate. The separated organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuo to form (2S) -N- (2-tetrahydropyranyloxy) -2- [5- [3- [ 2-hydroxyethylamino) acetylamino) phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (100 mg) as an amorphous solid. NMR (CDC13, d): 1.38-1.77 (6H, m), 1.89-2.00 (2H, m), 2.05-2.24 (2H, m), 2.68-2.91 (4H, m), 3.00-3.18 (4H, m) ), 3.29-3.52 (3H, m), 3.62-3.80 (3H, m), 4.53 (0.5H, s), 4.62 (0.5H, s), 7.22-7.32 (4H, m), 7.59-7.67 (H) , m), 7.69-7.75 (HH, m), 8.01 (HH, s), 9.48 (HH, s) MS (ESI-): 564 (MH) Example 250 1,1-Dioxide of (2S) - N- (2-tetrahydropyranyloxy) -2- (5- [3- [(4-morpholino) acetylamino) phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide ( 96 mg) in a manner similar to that of Example 249. NMR (CDCl 3, d): 1.40-1.56 (4H, m), 1.61-1.73 (2H, m), 1.89-2.01 (2H, m), 2.06-2.32. (2H,), 2.61-2.87 (6H, m), 3.05-3.19 (4H, m), 3.31-3.51 (HH, m), 3.62-3.74 (HH, m), 3.77- 3.65 (4H, m ), 4.53 (0.5H, s), 4.81 (0.5H, s), 7.25-7.31 (2H, m), 7.33-7.38 (2H,), 7.52-7.61 (ÍH,), 7.74-7.80 (ÍH, m ), 8.00- 8.41-3 (HH, m), 9.10 (HH, s) MS (ESI-): 590 (MH) The following compounds were obtained in a manner similar to that of Example 5 4. Example 251 1,1-dioxide (2 S) -N-hydroxy-2- [5- (4-aminocarb onyl phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran -2-acetamide (40 mg) NMR (DMSO-ds, d): 1.74-2.04 (4H, m), 2.37-2.46 (HH, m), 2.96-3.27 (4H, m), 3.4-3.54 ( HH, m), 7.25 (HH, d, J = 4.0Hz), 7.48 (HH, br), 7.59 (HH, d, J = 4.0Hz), 7.74 (2H, d, J = 7.5Hz), 7, 92 (2H, d, J = 7.5Hz), 8.02 (1H, br), 8.85 (1H, br) MS (ESI-): 407.1 (MH) Example 252 1, 1-dioxide (2S) -N-hydroxy -2- [5- (4-benzylaminocarbonyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (20 mg) NMR (DMSO-d6, d) : 1.74-2.08 (4H, m), 2.37-2.45 (HH, m) 1.95-3.26 (4H,), 3.43-3.52 (HH, m), 4.49 (2H, d, J = 6.0Hz), 7.24 (2H) , m), 7.31-7.34 (4H, m), 7.61 (HI, d, J = 3.0Hz), 7.75 (2H, d, J = 7.5Hz), 7.95 (2H, d, J = 7.5Hz), 8.84 (HH, s), 9.10 (HH, t, J = 6.0Hz) MS (ESI +): 523.1 (M + H + Na) Example 253 1, 1-dioxide (2S) -N-hydroxy-2 - [5 - (3- (ethoxycarbonylamino) phenyl) -2-thienyl] -3, 4, 5 , 6-tetrahydro-2H-thiopyran-2-acetamide (115 mg) NMR (DMSO-ds, d): 1.28 (3H, t, J = 7.0Hz), 1.73-2.05 (4H, m), 2.37-2.45 ( HH, m), 2.96-3.25 (4H, m), 3.42-3.53 (HH, m), 4.15 (2H, q, J = 7.0Hz), 7.20 (HH, d, J = 4.0Hz), 7.28-7.34 (3H, m), 7.48 (IH, d, J = 4.0Hz), 7.82 (IH, s), 8.84 (IH, br), 9.85 (IH, s), 10.60 (IH, br) MS (ESI-) : 451.2 (MH) EXAMPLE 254 (2S) -N-Hydroxy-2- [5- (3- (benzylaminocarbonyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydroxy-1,2-dioxide 2H-thiopyran-2-acetamide (50 mg) NMR (DMSO-d6, d): 1.73-2.05 (4H, m), 2.36-2.47 (H, m), 20 2.95-3.25 (4H, m), 3.41- 3.52 (HH, m), 4.31 (2H, d, J = 7.0Hz), 6.68 (HH, t, J = 7.0Hz), 7.18-7.38 (10H, m), 7.86 (HH, s), 8.72 (HH, s), 8.84 (HH, s) MS (ESI-): 512.3 (MH) Example 255 (2S) -N-hydroxy-2- [5- (3- (n-propyloxycarbonylamino) 1,1-dioxide ) -phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (120 mg) NMR (DMSO-ds), d): 0.95 (3H, t, J = 7.0Hz), 1.66 (2H, qt, J = 7.0, 7.0Hz), 1.72-2.05 (4H, m), 2.35-2.46 (HI, m), 2.94- 3.29 (4H, m), 3.40- 3.53 (HH, m), 4.05 (2H, t, J = 7.0Hz), 7.20 (HH, d, J = 4.0Hz), 7.29-7.34 (3H, m), 7.38 (HH, d, J = 4.0Hz), 7.83 (HH, s), 8.83 (HH, s), 9.73 (HH, s), 10.59 (HH, s) MS (ESI-): 465.3 (MH) Example 256 1, 1 (2S) -N-hydroxy-2- [5- (3- (isopropoxycarbonylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (90 mg) NMR (DMSO-ds, d): 1.26 (6H, d, J = 6.0Hz), 1.74- 2.04 (4H, m), 2.35-2.55 (H, m), 2.94-3.25 (4H, m ), 3.40-3.51 (HH, m), 4.40 (HH, qq, J = 6.0, 6.0Hz), 7.20 (HH, d, J = 4.0Hz), 7.29-7.33 (3H, m), 7.36 (HH, d, J = 4.0Hz), 7.85 (HH, s), 8.83 (HH, s), 9.67 (HH, s), 10.59 (1H, s) MS (ESI-): 465.3 (MH) Example 257 1.1 - (2S) -N-hydroxy-2- [5-] dioxide. { 3- (2-chloroethoxycarbonylamino) -phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (100 mg) NMR (DMSO-d6, d): 1.75-2.05 (4H, m), 2.36-2.47 (H) , m), 2 .94-3.29 (4H, m), 3.42-3.52 (ÍH, m), 3.88 (2H, d, J = 6.0Hz), 4.35 (2H, d, J = 6.0Hz), 7.21 ( HH, d, J = 4.0Hz), 7.32-7.36 (2H, m), 7.40 (HH, d, J = 4.0Hz), 7.84 (HH, s), 8.83 (HH, s), 9.94 (HH, s ), 10.08 (HH, s) MS (ESI-): 485.2 (MH) Example 258 1 (1S-dioxide (2S) -N-hydroxy-2 - [5- (3-valeryl-aminophenyl) -2-thienyl) -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (102 mg) NMR (DMSO-ds, d): 0.91 (3H, t, J = 8Hz), 1.24-1.41 (2H, m) , 1.52-1.66 (21H, m), 1.69-2.08 (4H, m), 2.33 (2H, t, J = 8Hz), 2.32-2.48 (ÍH, m), 2.92-3.26 (4H, m), 3.37- 3.54 (HH, m), 7.20 (HH, d, J = 3Hz), 7.34 (2H, d, J = 3Hz), 7.40 (HH, d, J = 3Hz), 7.42-7.5.2 (HH, m) , 7.99 (OH, s), 10.00 (OH, s), 10.60 (OH, s) MS (ESI-): 463 (MH) Example 259 1, 1-dioxide (2S) -N-hydroxy-2- [ 5- (3- (ethylthiocarbonylamino) -phenyl) -2-thienyl] -3,4,5,6-tetrahyd o- 2H-thiopyran-2-acetamide (92 mg) NMR (DMSO-ds, d): 1.26 (3H, t, J = 8Hz), 1.72-2.08 (4H, m), 2.36-2.49 (2H, m) , 2.89 (2H, q, J = 8Hz), 2.94-3.30 (4H, m), 3.39-3.55 (HH, m), 7.21 (HH, d, J = 3Hz), 7.32-7.44 (4H, m), 7.90 (H, s), 8.85 (H, s), 10.39 (H, s), 10.60 (H, s) MS (ESI +): 469 (M + H) Example 260 1,1-dioxide (2 S) -N-hydroxy -2 - [5- (3- (methylthiocarbonylamino) -phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (130 mg) NMR (DMS0- d6, d): 1.68-2.08 (4H, m), 2.33 (3H, s), 2.35-2.46 (HH,), 2.92-3.38 (4H, m), 3.39-3.53 (HH, m), 7.21 (HH) , d, J = 3Hz), 7.29-7.46 (4H, m), 7.90 (OH, s) MS (ESI-): 453 (MH) Example 261 1, 1-dioxide (2S) -N-hydroxy -2 - [5- (3- (benzyloxycarbonylamino) -phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (60.2 mg) NMR (DMSO-d6, d): 1.68 -2.07 (4H, m), 2.32-2.48 (HH, m), 2.92-3.34 (4H, m), 3.52-3.65 (HH, m), 5.18 (2H, s), 7.21 (HH, d, J = 3Hz), 7.26-7.50 (10H, m), 7. 85 (H, s), 9.91 (H, s), 10.60 (H, s) MS (ESI-): 513 (MH) Example 262 (2S) -N-hydroxy-2- [1,1-dioxide - (3- (2- (t-Butoxycarbonylamino) -acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetartide (40 mg) NMR (DMSO- d6, d): 1.40 (9H, s), 1.66-2.08 (4H, m), 2.35-2.48 (HH, m), 2.92-3.32 (4H, m), 3.45-3.53 (HH, m), 3.13 ( 2H, d, J = 7Hz), 7.07 (HH, t, J = 7Hz), 7.22 (HH, d, J = 3Hz), 7.32- 7.54 (4H, m), 7.97 (HH, a), 10.05 (HH) , s), 10.61 (4H, s) MS (ESI-): 536 (MH) Example 263 (2S) -N-hydroxy-2- [5- (3- (2- (4- chlorophenoxy) acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (90 mg) NMR (DMSO-d6, d): 1.71-2.09 (4H, m) , 2.35-2.49 (HH, m), 2.94-3.29 (4H, m), 3.42-3.55 (HH, m), 4.74 (2H, s), 7.00-7.12 (2H, m), 7.22 (H, br ), 7.32-7.47 (5H, m), 7.51-7.62 (HH, m), 8.02 (HH, s), 8.84 (HH, s), 10.22 (2H, s), 10.60 (HH, s) MS (ESI) -): 547 (MH) Example 264 1, 1-dioxide of (2S) -N-hydroxy-2- [5- (3- (phenoxy-carboni-lamino) -phenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (88) mg) NMR (DMSO-dg, d): 1.68-2.09 (4H, m), 2.32-2.48 (H), m), 2.92-3.30 (4H, m), 3.56-3.72 (H, m), 7.17-7.30 (4H, m), 7.31-7.51 (6H, m), 7.89 (H, s), 10.37 (H) , s), 10.61 (HH, s) MS (ESI-): 499 (MH) Example 265 (2S) -N-hydroxy-2- [5- (3- (2- (4- chlorophenyl) acetylamino) -phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (95 mg) NMR (DMSO-d6, d): 1.68-2.09 (4H, m), 2.35-2.48 (HH, m), 2.92-3.32 (4H, m), 3.54-3.66 (HH, m), 3.68 (2H, s) 7.20 (HH, d, J = 3Hz), 7.28 - 7.52 (8H, m), 7.99 (2H, s), 10.33 (HH, s), 10.60 (HH, s) MS (ESI-): 531 (MH) Example 266 (2S) - 1,1-dioxide - N-hydroxy-2- [5- (3- (2- (4-morpholinocarb onilamino) -acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2 -acetamide (50 mg) NMR (DMSO-ds, d): 1.71-2.08 (4H, m), 2.36-2.48 (HH, m), 2.94-3.62 (13H, m), 3.82 (2H, d, J = 7Hz), 6.96 (HH, t, J = 7Hz), 7.21 (HH, d, J = 3Hz), 7.31-7.49 (4H, m), 8.02 (HH, s), 8.84 (HH, br s) MS ( ESI-): 549 (MH) Example 267 1, 1-dioxide (2S) -N- hydroxy-2- [5- (3- (2- (N-ethyl-N-methylaminocarbonyloxy) acetylamino) phenyl) -2-thienyl] -3, 4,5,6-tetrahydro-2H-thiopyran-2-acetamide ( 133 mg) NMR (DMSO-d6, d): 1.05, 1.12 (3H, t, J = 8Hz), 1.68-2.07 (4H, m), 2.35-2.48 (H, m), 2.76-3.36 (9H,) , 3.39-3.54 (HH, m), 4.63 (2H, s), 7.21 (HH, d, J = 3Hz), 7.32-7.47 (4H, m), 8.00 (HH, s), 6.85 (HH, s) , 10.18 (HH, s), 10.61 (HH, s) MS (ESI-): 522 (MH) Example 268 1, 1-dioxide (2S) -N-hydroxy-2- [5- (3- ( isopropoxyacetylamino) -phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (204 mg) NMR (DMSO-d6, d): 1.78 (6H, d, J = 8Hz ), 1.72-2.08 (4H, m), 2.35-2.49 (HH, m), 2.94-3.31 (4H, m), 3.42-3.56 (HH, m), 3.63-3.77 (HH, m), 4.04 (2H) , s), 7.22 (HH, d, J = 3Hz), 7.32-7.43 (2H, m), 7.40 (HH, d, J = 3Hz), 7.56-7.64 (HH, m), 8.02 (HH, s) , 8.85 (H, s), 9.68 (H, s), 10.60 (H, s) MS (ESI +): 482 (M + H) Example 269 (2S) -N-hydroxy-2-1,1-dioxide [5- (3- (2- (2-oxo-l, 3-oxazolidi nil-3-yl) acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (480 mg) NMR (DMSO-d6, d) .1.65-2.09 ( 4H, m), 2.32-2.51 (ÍH, m), 2.88-3.53 (5H, m), 3.66 (2H, t, J = 8Hz), 4.04 (2H, s), 4.34 (2H, t, J = 8Hz), 7.21 (HH, d, J = 3Hz), 7.30-7.51 (4H, m), 8.03 (HH, s), 10.37 (HH, s), 10.62 (HH, s) MS (ESI- ): 506 (MH) Example 270 (2S) -N-hydroxy-2- [5- (3- (4-methoxyphenylaminocarbonylamino) phenyl) -2-thienyl] -3,5,6,6-dioxide -tetrahydro-2H-thiopyran-2-acetamide (140 mg) NMR (DMSO-d6, d): 1.73-2.04 (4H, m), 2.38-2.45 (H, m), 2.95-3.26 (4H, m), 3.39-3.54 (HH, m), 3.72 (3H, s), 6.86 (2H, d, J = 7.5Hz), 7.20 (HH, d, J = 4.0Hz), 7.23-7.32 (3H, m), 7.3 , 7 (2H, d, J = 7.5Hz), 7.50 (HH, d, J = 4.0Hz), 7.87 (HH, s), 8.50 (HH, s), 8.72 (HH, s), 8.84 (HH, s), 10.59 (OH, s) MS (ESI-): 528.3 (MH) Example 271 (2S) -N-hydroxy-2- [5- (3- (3-pyridin-1-aminocarbonyl) 1,1-dioxide amino) -phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2- acetamide (70 mg) NMR (DMSO-db, d): 1.75-2.05 (4H, m), 2.37-2.48 (HH, m), 2.96-3.25 (4H, m), 3.58-3.69 (HH, m), 7.21 (HH, d, J = 4.0Hz), 7.30-7.36 (3H, m), 7.42 (HH, d, J = 4.0Hz), 7.82 (HH, dd, J = 7.5, 5.0Hz), 7.90 (HH) , s), 8.29 35 (12H, d, J = 7.5Hz), 8.45 (HH, d, J = 5.0Hz), 9.03 (HH, s), 9.48 (HH, s), 9.85 (HH, s), 10.60 (OH, s) MS (ESI-): 499.2 (MH) Example 272 (2S) -N-hydroxy-2- [5- (3- (((2S) -2-) 1,1-dioxide hydrochloride aminopropionyl) amino) -phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (120 mg) of 1,1-dioxide (2S) -N- (2- tetrahydropyranyloxy) -2- [5-. { 3- (((2S) -2-tert-butoxy carboni laminopropionyl) amino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiop? Ran-2-acetamide NMR (DMSO-ds, d): 1.50 (3H, d, J = 7.0Hz), 1.72- 2.03 ( 4H, m), 2.35-2.46 (HH, m), 2.95-3.27 (4H, m), 3.43-3.54 (HH, m), 4.05 (HH, br t, J = 7.0Hz), 7.21 (HH, d , J = 4.0Hz), 7.37-7.43 (3H, m), 7.55 (HH, d, J = 7.5Hz), 7.95 (2H, s), 8.28-8.32 (3H, m), 10.63 (HH, s) , 10.81 (HH, s) MS (ESI-): 450.7 (MH) Example 273 1, (2S) -N-hydroxy-2- [5-. { 3- (((2R) -2- (tert-butoxycarbonylamino) propionyl) amino) phenyl} -2-thienyl] -3,, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (30 mg) NMR (DMSO-ds, d): 1.27 (3H, d, J = 6.0Hz), 1.38 (9H , s), 1.74-2.04 (4H, m), 2.37-2.42 (HH, m), 2.95-3.25 (4H, m), 3.38-3.51 (HH, m), 4.08-4.15 (HH, m), 7.10 (HH, d, J = 7.0Hz), 7.20 (HH, d, J = 4.0Hz), 7.31-7.36 (2H, m), 7.40 (HH, d, J = 4.0Hz), 7.50 (HH, br) , 7.96 (HH, s), 8.83 (HH, s), 10.04 (HH, s), 10.60 (HH, s) MS (ESI-): 550.3 (MH) Example 274 1,1-dioxide (2S) - N-hydroxy-2- [5-. { 3- (((2R) -2-aminopr opynyl) amino) -phenyl} -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (130 mg) of (2S) -N- (2-tetrahydropyranyloxy) -2- [5-dioxide] -. { 3 - (((2R) -2-tert-butoxycarbonylaminopropionyl) amino) phenyl} -2-thienyl] - 3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide NMR (DMSD-d6, d): 1.50 (3H, d, J = 7.0Hz), 1.72- 2.03 (4H, m), 2.35-2.46 (HH, m), 2.95-3.27 (4H, m), 3.43-3.54 (HH, m), 4.05 (HH, br t, J = 7.0Hz), 7.21 (HH, d , J = 4.0Hz), 7.37-1.43 (3H, m), 7.55 (HH, d, J = 7.5Hz), 7.95 (HH, s), 8.28-8.32 (3H, m), 10.63 (HH, s), 10.81 (HH, s) MS (ESI-): 452.1 (MH) Example 275 (2S) -N-hydroxy-2- [5-. { 3- (2- (4-methylphenoxy) -acetylamino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (150 mg) NMR (DMSO-d6, d): 1.74-2.04 (4H, m), 2.24 (3H, s ), 2.37-2.45 (HH, m), 2.95-3.26 (4H, m), 3.44-3.53 (HH, m), 4.67 (2H, s), 6.90 (2H, d, J = 7.5Hz), 7.11 ( 2H, d, J = 7.5Hz), 7.21 (HH, d, J = 4.0Hz), 7.34-7.37 (2H, m), 7.42 (HH, d, J = 4.0Hz), 7.56 (HH, d, J = 6.0Hz), 8.01 (HH, s), 8.62 (HH, s), 10.17 (HH, s), 10.59 (HH, s) MS (ESI-): 528.1 (MH) Example 276 1,1-dioxide (2S) -N-hydroxy-2- [5-. { 3- (2-N, N-dimethylamino) -acetylamino) phenyl} -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (95 mg) NMR (DMSO-d6, d): 1.14-2.05 (4H, m), 2.36-2.45 (H) , m), 2.89 (6H, s), 2.96-3.27 (4H, m), 3.44-3.54 (HH, m), 4.17 (2H, s), 7.22 (HH, d, J = 4.0Hz), 7.38- 7.42 (2H, m), 7.50 (IH, d, J = 5.0Hz), 7.95 (IH, s), 8.84 (IH, br), 9.22 (IH, br), 10.60 (IH, s), 10.821 (IH) , s) MS (ESI-): 464.3 (MH) Example 277 (2S) -N-hydroxy-2- [5- (3- (allyloxycarbonylamino) -phenyl) -2-thienyl 1,1-dioxide] -3 , 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (50 mg) NMR (DMSO-dg, d): 1.73-2.04 (4H, m), 2.36-2.45 (H, m), 2.95-3.25 (4H, m), 3.41-3.49 (HH, m), 4.63 (2H, d, J = 5.0Hz), 5.25 (HH, d, J = 8.0Hz), 5.38 (HH, d, J = 8.0Hz) , 5.93-6.06 (HH, m), 7.20 (HH, d, J = 4.0Hz), 7.30-7.35 (HH, m), 7.49 (HH, d, J = 4.0Hz), 7.84 (HH, s), 8.83 (H, s), 9.85 (H, s) MS (ESI-): 463.3 (MH) Example 278 (2S) -N-hydroxy-2- [5- (3-ethoxycarbonylmethylamine 1,1-dioxide) -carboni lamino) phenyl) -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopra-ran-2-acetamide (40 mg) NMR (DMSO-dg, d): 1.23 (3H, t, J = 7.5Hz), 1.73- 2.05 (4H, m), 2.36-2.47 (HH, m), 2.94-3.25 (4H, m), 3.42-3.54 (HH, m), 3.87 (2H, d, J = 7.0Hz), 4.13 (2H, q, J = 7.5Hz), 6.50 ( ÍH, t, J = 7.0Hz), 7.18 (HH, d, J = 4.0Hz), 7.21-7.30 (3H, m), 7.37 (HH, d, J = 4.0Hz), 7.63 (HH, s), 8.83 (HH, s), 8.96 (HH, s) MS (ESI-): 508.3 (MH) Example 279 (2 S) -N-hydroxy-2- [5- (3- (benzyloxy-acetylamino) 1,1-dioxide ) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (55 mg) NMR (DMSO-d6, d): 1.75-2.06 (4H, m), 2.36- 2.46 (HH, m), 2.95-3.25 (4H, m), 3.42-3.53 (HH, m), 4.11 (2H, s), 4.64 (2H, s), 7.21 (HH, d, J = 4.0Hz) , 7.26-7.43 (8H, m), 7.54-7.57 (ÍH, m), 8.01 (ÍH, s), 8.82 (ÍH, s), 9.90 (ÍH, s), 10.60 (ÍH, s) MS (ESI- ): 527.3 (MH) Example 280 (2S) -N-hydroxy-2- [5- (3- (cyclopentylcarbonyl-amino) -phenyl) -2-thienyl] -3,4,5,6-dioxide -tetrahydro-2H-thiopyran-2-acetamide (120 mg) NMR (DMSO-ds, d ): 1.52-2.06 (12H, m), 2.36-2.47 (HH, m), 2.78 (HH, tt, J = 7.0, 7.0Hz), 2.95- 3.25 (4H,), 3.40-3.54 (1H, m), 7.20 (HH, d, J = 4.0Hz), 7.32-7.34 (2H, m), 7.40 (HH, d, J = 4.0Hz), 7.45-7.49 (HH, m), 8.03 (HH) , s), 8.84 (ÍH, s), 9.98 (ÍHs, s), 10.61 (s, s) MS (ESI-): 475.3 (MH) EXAMPLE 281 (2S) -N-Hydroxy-2- [5- (3- ((2-hydroxyethyl) -aminocarbonylamino) phenyl) -2-thienyl 1,1-dioxide] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (20 mg) NMR (DMSO-ds, d): 1.72-2.04 (4H, m), 2.40-2.45 (H, m), 2.93 -3.25 (6H, m), 3.41-3.50 (3H, m), 4.75 (HH, t, J = 5.0Hz), 6.22 (HH, t, J = 5.0Hz), 7.16-7.25 (3H, m), 7.35 (HH, d, J = 4.0Hz), 7.82 (HH, s), 8.71 (HH, s), 8.83 (HH, s) MS (ESI-): 466.4 (MH) Example 282 1.1- Hydrochloride (2S) -N-hydroxy-2- [5- (3- ((2-aminoethoxy) carbonylamino) -phenyl) -2-thienyl] -3, 4,5,6-tetrahydro-2H-thiopyran-2 dioxide -acetamide (20 mg) NMR (DMS0-d6, d): 1.74-2.07 (4H, m), 2.35-2.44 (HH, m), 2.95-3.27 (4H, m), 3.48-3.66 (5H, m) , 7.12-7.51 (4H, m), 7.86-7.90 (2H, m), 8.00-8.08 (2H, m), 9.10 (H, s), 9.85 (H, s), 10.62 (H, s) MS ( ESI +): 468.3 (M + H) Example 283 (2S) -N-hydroxy-2- [5- (3- (3-chloropropionylamino) phenyl) -2-thienyl] -3,4-dioxide, 5, 6-tetrahydro-2H-thiopira n-2-acetamide (95 mg) NMR (DMSO-d6, d): 1.73-2.06 (4H, m), -2.37-2.46 (HH, m), 2.84 (2H, t, J = 6.0Hz), 2.95 -3.26 (4H, m), 3.43-3.56 (HH, m), 3.90 (2H, t, J = 6.0Hz), 7.21 (HH, d, J = 4.0Hz), 7.35-7.40 (2H, m), 7.42 (HH, d, J = 4.0Hz), 7.47-7.52 (HH, m), 8.00 (HH, s), 8.85 (HH, s) MS (ESI-): 469.1 (MH) Example 284 1, 1- (2S) -N-hydroxy-2- [5- (4- (methanesulfonylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide dioxide (40 mg) NMR (DMSO-d6, d): 1.72-2.05 (4, H, m), 2.34-2.44 (HH, m), 2.89 (3H, s), 2.93-3.23 (4H, m), 3.41-3.51 (HH) , m) 7.12 (2H, d, J = 7.5Hz), 7.15 (IH, d, J = 4.0Hz), 7.31 (IH, d, J = 4.0Hz), 7.50 (2H, d, J = 7.5Hz) MS (ESI-): 457.3 (MH) EXAMPLE 285 (2S) -N-Hydroxy-2- [5- (4- (2- (phenylaminocarbonyl) -ethenyl) phenyl) -2-thienyl 1,1-dioxide] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (40 mg) NMR (DMSO-d6, d): 1.73-2.07 (4H, m), 2.38-2.48 (H, m), 2.97 -3.54 (5H, m), 6.86 (HH, d, J = 16Hz), 7.06 (HH, J = 8.0, 8.0Hz), 7.24 (HH, d, J = 4.0Hz), 7.34 (2H, dd, J = 8.0, 8.0Hz), 7.56 (HH, d, J = 4.0Hz), 7.61 (HH, d, J = 16Hz), 7.65-7.75 (6H, m), 8.85 (OH, s), 10.2 (OH, s), 10.6 (OH, s) Example 286 (2S) -N-hydroxy-1,1-dioxide 2- [5- (4- (2- (4-methoxyphenylaminocarbonyl) ethenyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (100 mg) NMR ( DMSO-ds, d): 1.72-2.07 (4H, m), 2.37-2.46 (HH, m), 2.97-3.52 (5H, m), 3.7 4 (3H, s) 6.03 (HH, d, J = 16Hz ), 6.92 (2H, d, J = 8.5Hz), 7.24 (HH, d, J = 4.0Hz), 7.54-7.75 (8H, 8 .85 (HH, s), 10.08 (HH, s), 10.6 ( ÍH, s) Example 287 (2S) -N-hydroxy-2- [5- (4- (2- (4-fluorophenylaminocarbonyl) ethenyl) phenyl) -2-thienyl] -3,4-dioxide, 5,6-tetrahydro-2H-thiopyran-2-acetamide (80 mg) NMR (DMSO-ds, d): 1.73-2.07 (4H, m), 2.37-2.46 (H, m), 2.98-3.53 (5H, m), 6.83 (ÍH, d, J = 16Hz), 17.18 (2H, dd, J = 8.5, 8.5Hz), 7.24 (2H, d, J = 4.0Hz), 7.57-7.75 (8H, m), 8.8 5 (ÍH, s), 10.3 (ÍH, s), 10.6 (ÍH, s) Example 288 1,1-di (2S) -N-hydroxy-2- [5- (4- (ethylcarbonyloxy) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (100 mg) oxide NMR (DMSO-d6, d): 1.13 (3H, dd, J = 7.5, 7.5Hz), 1.71- 2.07 (4H, m), 2.36-2.46 (HH, m), 2.62 (2H, ddd, J = 7.5 , 7.5, 7.5Hz), 2.96-3.52 (5H, m), 7.20-7.21 (3H, m), - 7.46 (ÍH, d, J = 4.0Hz), 7.68 (2H, d, J = 8.5Hz), 8.85 (1H, s) MS (ESI-): 436 (MH) EXAMPLE 289 1 (1S-dioxide-2-N-hydroxy-2- [5- (4- (methyloxycarbonylaminomethyl) -phenyl) -2-thienyl ] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (45 mg) NMR (DMSO-dg, d): 1.70-2.06 (4H, m), 2.35-2.45 (H, m), 2.96-3.50 (5H,), 3.56 (3H, s), 4.19 (2H, d, J = 7.0Hz), 17.20 (ÍH, d, J = 4.0Hz), 7.29 (2H, d, J = 8.5Hz) , 7.43 (HH, d, J = 4.0Hz), 7.60 (2H, d, J = 8.5Hz), 7.70 (HH, t, J = 7.0Hz), 8.85 (HH, s), 10.60 (HH, s) MS (ESI-): 451 (MH) EXAMPLE 290 1,1-Dioxide (2S) -N-hydroxy-2- [5- (4 - (ethylcarbonylmethoxy) phenyl) -2-thienyl] -3,, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (120 mg) NMR (DMSO-d6, d): 0.98 (3H, t, J = 7.2Hz), 1.70- 2.07 (4H,), 2.33-2.45 (ÍH, m), 2.54 (2H, q, J = 7.2Hz), 2.95-3.50 (5H, m), 4.86 (2H, s), 6.95 (2H, d, J = 8.5Hz), 7.16 (HH, d, J = 4.0Hz), 7.34 (HH, d, J = 4.0Hz), 7.55 (2H, d, J = 6.5Hz), 8.84 (HH, br) MS (ESI-): 450 ( MH) EXAMPLE 291 (2S) -N-Hydroxy-2- [5- (4- (cyclopropylaminocarbonyl-methoxy) f-enyl) -2-thienyl] -3, 4, 5, 6-tetrahydroxy-dioxide 2H-thiopyran-2-acetamide (70 mg) NMR (DMSO-ds, d): 0.46-0.51 (2H, m), 0.60-0.66 (2H, m), 1.70-2.07 (4H, m), 2.34-2.45 (HH, m), 2.66-2.75 (HH, m), 2.95-3.50 (5H, m), 4.47 (2H, s), 6.99 (2H, d, J = 8.5Hz), 7.16 (HH, d, J = 4.0Hz), 7.35 (HH, d, J = 4.0Hz), 7.57 (2H, d, J = 8.5Hz), 8.15 (HH, br), 8.84 (HH, s), 10.59 (HH, s) Example 292 (2S) -N-hydroxy-2- [5- (4- (n-propylaminocarbonylmethoxy) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran- 1,1-dioxide 2-acetamide (70 mg) NMR (DMSO-ds, d): 0.62 (3H, t, J = 7.5Hz), 1.39-1.50 (2H, m), 1.73-2.07 (4H, m), 2.35-2.45 ( ÍH,), 2.95-3.52 (7H, m), 4.50 (2H, s), 7.01 (2H, d, J = 8.5Hz), 7.17 (HH, d, J = 4.0Hz), 7.35 (HH, d, J = 4.0Hz), 7.58 (2H, d, J = 13.5Hz), 8.11 ( ÍH, br), 8.85 (HH, s), 10.59 (HH, s) MS (ESI-): 479 (MH) Example 293 1, 1-dioxide (2S) -N-hydroxy-2- [5- ( 3-hydroxyphenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (120 mg) NMR (DMSO-ds, d): 1.70-2.05 (4H, m), 2.36 -12.45 (HH, m), 2.95-3.50 (5H, m), 6.71-6.74 (HH, m), 7.00 (1H, s), 7.06 (HH, d, J = 8.0Hz), 7.17-7.25 (2H , m), 7.39 (HH, d, J = 4.0Hz), 8.85 (HH, s), 9.62 (HH, s), 10.60 (HH, s) MS (ESI-): 380 (MH) Example 294 1, 1-dioxide (2S) -N-hydroxy-2 - [5- (3-butylaminocarbonylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (170 mg ) NMR (DMSO-ds, d): 0.90 (3H, dd, J = 7.2, 7.2Hz), 1.27-1.37 (2H, m), 1.37-1.47 (2H, m), 1.70- 2.05 (4H, m) , 2.37-2.45 (HH, m), 2.95-3.50 (7H, m), 6.16 (HH, dd, J = 7.0, 7.0Hz), 7.17- 7.28 (4H, m), 7.37 (HH, d, J = 4.0Hz), 7.84 (ÍH, s), 8.55 (ÍH, s), 10.6 (ÍH, s) MS (ESI-): 478 (MH) Example 295 (2S) -N-hydroxy-2- [5- (3- (1-naphthyl) aminocarbonylamino) phenyl) -2-thienyl 1,1-dioxide] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (250 mg) NMR (DMSO-d6, d): 1.72-2.07 (4H, m), 2.38-2.47 (H, m), 2.95 -3.31 (5H, m), 7.22 (HH, d, J = 4.0Hz), 7.29-7.37 (3H, m), 7.44 (HH, d, J = 4.0Hz), 7.47-7.68 (4H, m), 7.94-7.96 (2H, m), 8.02 (HH, d, J = 8.3Hz), 8.15 (HH, d, J = 8.3Hz), 8.85 (HH, s), 9.27 (HH, s), 10.6 (HH) , s) MS (ESI-): 548 (MH) EXAMPLE 296 (2S) -N-Hydroxy-2- [5- (3- (allylaminocarbonylamino) phenyl) -2-t-enyl] -1-dioxide] - 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (200 mg) NMR (DMSO-dg, d): 1.70-2.07 (4H, m), 2.36-2.45 (H, m), 2.96- 3.25 (5H, m), 3.72-3.76 (2H,), 5.02-5.19 (2H, m), 5.80-5.94 (HH, m), 6.29-6.32 (HH, m), 7.18-7.26 (4H, m), 7.36 (HH, d, J = 4.0Hz), 7.84 (HH, s), 6.68 (HH, s), 10.6 (1H, s) MS (ESI-): 462 (MH) Example 297 1, 1 - (2S) -N-hydroxy-2- [5- (3- ( isobut i 1 ami noc to rboni lamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (170 mg) NMR (DMSO-d6, d): 0.88 (6H , d, J = 6.6Hz), 1.65- 2.07 (5H, m), 2.40-2.47 (HH, m), 2.94 (2H, dd, J = 6.5, 6.5Hz), 3.00-3.50 (5H, m), 6.23 (ÍH, dd, J = 6.5, 6.5Hz), 7.17-7.20 (3H, m), 7.37 (2H, d, J = 4.0Hz), 7.84 (IH, s), 8.54 (IH, s), 10.6 (HH, s) MS (ESI-): 478 (MH) EXAMPLE 298 1 (1 S) - (2 S) -N-Hydoxoxy-2- [5- (3- (cyclohexylmethylaminocarbonyl-amino) phenyl) -2- thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (110 mg) NMR (DMSO-d6, d): 0.83-0.95 (2H, m), 1.11-1.25 (3H, 1.60- 1.75 (6H, m), 1.63-2.07 (4H, m), 2.37-2.45 (HH, m), 2.93-3.07 (4H, m), 3.08- 3.30 (3H, m), 6.22 (HH, br), 7.19-7.28 (4H, m), 7.37 (1H, d, J = 4.0Hz), 8.55 (IH, s), 10.6 (IH, s) MS (ESI-): 518 (MH) Example 299 1.1- (2S) -N-hydroxy-2- [5- (3- (2-methoxy-tilamino-carbon-lamino) phenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2 dioxide -acet amide (150 mg) NMR (DMSO-d6, d): 1.71-2.06 (4H, m), 2.37-2.46 (1H), m), 2.95-3.01 (2H, m), 3.05-3.25 (3H, m), 3.28 (3H, s), 3.35-3.51 (4H, m), 6.21-6.25 (HI, m), 7.16-7.25 (4H, m), 7.37 (HH, d, J = 4.0Hz), 7.83 (HH, s), 8.68 (HH, s), 8.79-6.86 (HH, br), 10.6 (1H, s) MS (ESI) -): 480 (MH) Example 300 (2S) -N-hydroxy-2- [5- (3- (N-methyl-N-ethylaminocarbonyl) amino) phenyl) -2-thienyl 1,1-dioxide] - 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (55 mg) NMR (DMSO-ds, d): 1.08 (3H, t, J = 7.0Hz), 1.70-2.08 (4H, m) , 2.37-2.45 (HH, m), 2.94 (3H, s), 2.97-3.54 (7H,), 7.20 (HH, d, J = 4.0Hz), 7.25 (2H, d, J = 8.0Hz), 7.37 (HH, d, J = 4.0Hz), 7.45 (2H, d, J = 8.0Hz), 7.64 (HH, s), 8.84 (HH, s), 10.59 (HH, s) MS (ESI-): 464 (MH) Example 301 (2S) -N-Hydroxy-2- [5- (4- (2- (N, N-dimethylaminocarbonyl) -ethenyl) phenyl) -2-thienyl] -3-dioxide , 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (180 mg) NMR (DMSO-d6, d): 1.70-2.08 (4H, m), 2.37-2.45 (H, m) 2.93 (3H, s), 2.94-3.10 (2H, m), 3.17 (3H, s), 3.18-3.55 (3H, m), 7.20 (ÍH, d, J = 4.0Hz), 7.25 (HH, d, J = 16Hz), 7.45 (HH, d, J = 16Hz), 7.55 (HH, d, J = 4.0Hz), 7.66 (2H, d, J = 8.5Hz), 7.75 (2H, d, J = 8.5Hz), 8.84 (IH, br), 10.60 (IH, s) MS (ESI-): 461 (MH) Example 302 1,1-dioxide (2S) -N-hydroxy-2- [5- (4- (2- (isopropylaminocarbonyl) -ethenyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (110 mg) NMR (DMSO-ds, d): 1.11 (6H, d, J = 6.5Hz), 1.70-2.07 (4H, m), 2.36-2.44 (HH, m), 2.97-3.55 (5H, m), 3.40-4.00 (HH, m), 6.62 (HH, d, J = 16Hz), 7.23 (HH, d, J = 4.0Hz), 7.40 (HH, d, J = 16Hz), 7.55 (HH, d, J = 4.0Hz), 7.58 (2H, d, J = 8.5Hz), 7.69 (2H, d, J = 8.5Hz), 7.99 (IH, d, J = 7.5Hz), 10.6 (IH, s) MS (ESI -): 475 (MH) Example 303 (2S) -N-hydroxy-2- [5- (4- (2- (propylaminocarbonyl) -ethenyl) phenyl) -2-thienyl] -3-dioxide] , 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (120 mg) NMR (DMSO-d6, d): 0.88 (3H, t, J = 7.5Hz), 1.47 (2H, q, J = 7.5 Hz), 1.70-2.07 (4H, m), 2.35- 2.45 (ÍH, m), 2.96-3.55 (7H, m), 6.65 (HH, d, J = 16Hz), 7.23 (HH, d, J = 4.0Hz), 7.40 (HH, d, J = 16Hz), 7.55 (HH, d, J = 4.0Hz), 7.60 (2H, d , J = 8.5Hz), 7.69 (2H, d, J = 8.5Hz), 8.10 (IH, t, J = 7.0Hz), 10.6 (IH, s) MS (ESI-): 475 (MH) Example 304 1, 1 (2S) -N-hydroxy-2- [5- (4- (methylaminocarbonyloxy) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyranyl-2-acetamide (150 mg) NMR (DMSO-d6, d): 1.71-2.05 (4H, m), 2.35-2.45 (HH, m), 2.67 (3H, d, J = 4.5Hz), 2.95-3.51 (5H, m ), 7.15 (2H, d, J = 7Hz), 7.21 (IH, d, J = 4.0Hz), 7.43 (IH, d, J = 4.0Hz), 7.63 (2H, d, J = 8.7Hz), 7.65 -7.68 (HH, m), 8.85 (HH, s), 10.6 (HH, s) MS (ESI-): 437 (MH) Example 305 (2S) -N-hydroxy- 2 - [1,1-dioxide] 5- (4- (ethylaminocarbonyloxy) phenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (130 mg) NMR (DMSO-ds, d): 1.08 (3H, dd, J-7.2, 7.2Hz), 1.71-2.05 (4H, m), 1.85-1.96 (HH, m), 2.95-3.30 (6H, m), 3.41-3.53 (HH, m), 7.15 (2H, d, J = 8.7Hz), 7.20 (lH d, J = 4.0Hz), 7.43 (lH, d, J = 4.0Hz), 7. 63 (2H, d, J = 8.7Hz), 7.80 (IH, dd, J = 7.0, 7.0Hz), 8.85 (IH, s), 10.6 (IH, s) MS (ESI-): 451 (MH) Example 306 (2S) -N-hydroxy-2- [5- (5-acetyl-2-thienyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-1,1-dioxide -acetamide (20 mg) NMR (DMSO-ds, d): 1.68-2.07 (4H, m), 2.35-2.45 (HH, m), 2.53 (3H, s), 2.95-3.53 (5H, m), 7.21 (HH, d, J = 4.0Hz), 7.44 (HH, d, J = 4.0Hz), 7.51 (HH, d, J = 4.0Hz), 7.91 (HH, d, J = 4.0Hz), 8.85 (HH) , s) MS (ESI-): 412 (MH) The following compounds were obtained in a manner similar to that of Example 166. EXAMPLE 307 1,1-Dioxide (2S) -N-hydroxy-2- [5- ( 4-methoxyacetoxy) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (100 mg) NMR (DMSO-ds, d): 1.71-2.05 (4H, m) , 2.36-2.45 (HH, m), 2.97-3.28 (4H, m), 3.41 (3H, s), 3.42-3.51 (HH, m), 4.36 (2H, s), 7.21 (HH, d, J = 4.0Hz), 7.22 (2H, d, J = 8.5Hz), 7.48 (IH, d, J = 4.0Hz), 7.70 (2H, d, J = 8.5Hz), 8.84 (IH, s) MS (ESI- ): 452 (MH) Example 308 1,1-dioxide ( 2S) -N-hydroxy-2- [5- (4- (ethoxycarbonyloxy) phenyl) -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (80 mg) NMR (DMSO-d6, d): 1.31 (3H, dd, J = 7.5, 7.5Hz), 1.70-1.93 (4H, m ), 2.36-2.47 (ÍH, m), 2.97- 3.51 (5H, m), 4.27 (2H, ddd, J = 7.5, 7.5, 7.5Hz), 7.21 (ÍH, d, J = 4.0Hz), 7.30 ( 2H, d, J = 6.5Hz), 7.49 (HH, d, J = 4.0Hz), 7.69 (2H, d, J = 8.5Hz) MS (ESI-): 452 (MH) Example 309 1, 1-dioxide of (2S) -N-hydroxy-2- [5- (4 - (cyclopropylcarbonyloxy) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (100 mg) NMR (DMSO-d6, d): 1.03-1.06 (4H, m), 1.70-2.05 (5H, m), 2.36-2.47 (2H, m), 2.95-3.51 (5H, m), 7.17-7.21 (3H, m), 7.46 (HH, d, J = 4.0Hz), 7.66 (2H, d, J = 8.5Hz), 8.84 (HH, s), 10.58 (HH, s) MS (ESI-): 448 (MH) EXAMPLE 310 (1S) -N-hydroxy-2- [3- (4 - (ethoxycarbonylmethoxy) -phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran 2-acetamide (150 mg) NMR (DMSO-d6, d): 1.22 (3H, t, J = 7.2Hz), 1.70-2.07 (4H, m), 2.35-2.45 (HH, m), 2.95-3.52 ( 5H, m), 4.17 (2H, q, J = 7.2Hz), 4.8 2 (2H, s), 6.97 (2H, d, J = 8.5Hz), 7.16 (IH, d, J = 4.0Hz), 7.34 (IH, d, J = 4.0Hz), 7.56 (2H, d, J = 8.5Hz), 8.83 (OH, s), 10.6 (OH, s) Example 311 To a solution of 0.4 M 4-chlorophenyl isocyanate (192 mg) in dichloromethane (2.5 ml) were added N- [2- [2 - (5- (3-aminophenyl) -2-thienyl) -l, l-dioxo-3,4,6,6-tetrahydro-2H-thiopyran-2-yl) acetyl] hydroxylaminetrityl (26 μmol, 13.2 μmol / crown x 2). The reaction mixture was allowed to stand overnight at room temperature. The crowns were washed successively with N, N-dimethylformamide, methanol and dichloromethane. The crowns were treated with 5% trifluoroacetic acid in dichloromethane for 1 hour at room temperature and removed from the solution. Then, the solution was evaporated under a stream of nitrogen, the residue was purified by reverse phase HPLC (0.1% trifluoroacetic acid in acetonitrile, gradient 10-40%) to form (2S) -N-hydroxy 1,1-dioxide -2- [5- (3- (4-chloro-phenylaminocarbonyl-lamino) phenyl) -2-thiyl-enyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (1.6 mg) as a powder White . MS (ESI +): 551.3 (M + H + NH3) The following compounds were obtained in substantially the same manner as that of Example 311. Example 312 (2S) -N-hydroxy-2- [1,1-dioxide] - (3- (n-Phenylaminocarbonylamino) -3,4,5,6-tetrahydro-2H-thiopyran-2-phenyl) -2-thienyl] acetamide (1.2 mg) MS (ESI-): 492.3 (MH) Example 313 (2S) -N-hydroxy-2- [5- (3- (n-hexylaminocarbonyllamino) -phenyl) -2-thienyl] -3, 4, 5, 6-tetrahydro-2H- 1,1-dioxide thiopyran-2-acetamide (3.0 mg) MS (ESI-): 506.4 (MH) Example 314 (2S) -N-hydroxy-2- [5- (3- (3-chlorofenylaminocarbonylamino) phenyl) 1,1-dioxide ) -2-thienyl] -3, 4,5,6-tetrahydro-2H-thiopyran-2-acetamide (1.3 mg) MS (ESI +): 550.7 (M + H + NH3) E j empl o 315 Hydrochloride (2S) -N-hydroxy-2- [5- (3- (((R) -2-amino-2-f-enylacetyl) amino) phenyl) -2-thienyl] -3-dioxide,, 5,6-tetrahydro-2H-thiopyran-2-acetamide (76 mg) in the same manner as that of Example 54 NMR (DMSO-d 5, d): 1.64-2.11 (4H, m), 2.32-2.98 (1H, m), 2. 87-3.62 (5H, m), 5.30 (ÍH, br s), 7.22 (ÍH, s), 7.34-7.82 (10H, m), 7.97 (ÍH, s), 8.91 (2H, br s), 7.97 ( HH, s) 10.66 (HH, br s), 11.27 (HH, s) MS (ESI +): 514 (M + H) Example 316 1,1-dioxide of (2S) -N-hydroxy-2- [ 5- (3- (3- (benzoylamino) -propionylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (96 mg) in a manner similar to that of Example 199. NMR (DMSO-d6, d): 1.64-2.10 (4H, m), 2.33-2.48 (HH,), 2.58-2.76 (2H, m), 2.88-3.56 (9H, m), 7.21 (HH) , br s), 7.30-7.64 (8H, m), 7.84 (2H, br s), 8.03 (ÍH, br s), 8.64 (ÍH, br s) MS (ESI-): 554 (MH) EXAMPLE 317 (2S) -N-Hydroxy-2- [5- (3- (3- (ethylaminocarbonylamino) -propionylamino) phenyl) -2-dioxide was obtained. thienyl] - 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (98 mg) in a manner similar to that of Example 199. NMR (DMSO-ds, d): 0.96 (3H, t, J = 7Hz), 1.69-2.10 (4H, m), 2.33-2.48 (HH, m), 2.90-3.64 (11H, m), 7.19 (HH, d, J = 3Hz), 7.28-7.51 (5H, m) , 8.04 (OH, s) MS (ESI-): 521 (MH) EXAMPLE 318 (2S) -N-Hydroxy-2- [5- (3- (3- (metansulphonylamino) 1,1-dioxide was obtained. ) -propionylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (54 mg) in a manner similar to that of Example 199. NMR (DMSO-d6, d ): 1.22-2.12 (4H, m), 2.35-2.49 (ÍH, m), 2.58 (2H, t, J = 7Hz), 2.99 (3H, s), 2.94-3.62 (7H, m), 7.06-7.16 (ÍH, m), 7.22 (ÍH, d, J = 3Hz), 7.33-7.39 (2H,), 7.40 (ÍH, d, J = 3Hz), 7.43-7.52 (ÍH, m), 8.01 (ÍH, s ) MS (ESI-): 528 (MH) EXAMPLE 319 (2S) -N-Hydroxy-2- [5-1-] -hydroxy chloride was obtained (3- ((4-piper idini loxi) acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (55 mg) of 1,1-dioxide (2S ) -N- (2-tetrahydropyranyloxy) -2- [5- (3- ((1-tert-butoxycarbonyl-4-piperidinyloxy) acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro- 2H-thiopyran-2-acetamide in a manner similar to that of Example 54. NMR (DMSO-d6, d): 1.68-2.11 (8H,), 2.34-2.98 (H, m), 2.89-3.56 (8H, m ), 3.66-3.80 (HH, m), 4.14 (2H, s), 7.11-7.62 (5H, m), 8.00 (HH, s), 8.85 (HH, s), 9.83 (HH, s), 10.60 ( ÍH, s) MS (ESI +): 522 (M + H) The following compounds were obtained in a manner similar to that of Example 89. EXAMPLE 320 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) - 2- [5- (4- (methanesulfonylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (70 mg) NMR (CDC13, d): 1.32 (2H , br), 1.40-1.49 (2H, m), 1.64-1.68 (2H, m), 1.94 (2H, br), 2.10- 2.20 (2H,), 2.76-2.80 (2H, m), 3.00 (2H, s), 3.06-3.10 (2H, m), 3.15 (2H, b r), 3.33- 3.51 (ÍH, m), 3.65-3.74 (ÍH, m), 4.55 (1 / 2H, br), 4.82 (1 / 2H, br), 7.01 (ÍH, br), 7.11- 7.16 ( 3H, m), 7.45 (2H, d, J = 7 .5Hz), 8.25 f (1 / 2H, s), 8.33 (1 / 2H, s) MS (ESI-): 541.4 (MH) 5 Example 321 1 , (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (methoxycarbonylaminomethyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran 2-acetamide (80 mg) NMR (DMSO-ds, d): 1.37 (6H, m), 1.69-1.81 (2H, lf), 1.82-2.07 (2H, m), 2.35-2.45 (H, m), 2.90-3.50 (6H, m), 3.57 (3H, s), 3.72-3.88 (HH, m), 4.20 (2H, d, J = 7.0Hz), 4.45, 4.75 (HH, s), 7.20-7.22 ( HH, m), 7.28 (2H, d, J = 8.5Hz), 7.41-7.43 (HH, m), 7.61 (2H, d, 15 J = 8.5Hz), 7.72 (HH, t, J = 7.0Hz) MS (ESI-): 535 (MH) EXAMPLE 322 ^^ 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (cyclopropylcarbonyloxy) phenyl) -2-thienyl] -3, 4, 5, 6-20 tetrahydro-2H-thiopyran-2-acetamide (150 mg) NMR (DMSO-ds, d): 1.03-1.07 (4H, m), 1.39-1.64 (6H, m), 1.70-2.05 (5H, m), 2.35-2.4 5 (ÍH,), 2.90-3.51 (6H, m), 3.75-3.90 (ÍH, m), 4.45, 4.75 (ÍH, s), 7.02-7.05 (ÍH, m), 7.19 5 (2H, d, J = 8.5Hz), 7.44-7.47 (ÍH, m), 7.76 (2H, d, J = 8.5Hz) Example 323 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (ethoxycarbonylmethoxy) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (220 mg) NMR (DMSO-d6, d): 1.22 (3H, t, J = 7.0Hz), 1.35- 1.62 (6H, m), 1.66-2.05 (4H, m), 2.35-2.45 (HH, m), 2.90-3.50 (6H, m), 3.73-3.90 (HH, m) , 4.18 (2H, q, J = 7.0Hz), 4.45, 4.75 (ÍH, s), 4.82 (2H, s), 6.96 (2H, d, J = 8.5Hz), 7.16-7.21 (ÍH, m), 7.32-7.36 (HH, m), 7.57 (2H, d, J = 8.5Hz) Example 324 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (ethylcarboni lme toxy) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (200 mg) NMR (DMSO-d6, d): 0.98 (3H, t, J = 7.2 Hz), 1.35- 1.65 (6H, m), 1.67-2.05 (4H, m), 2.32-2.45 (HH, m), 2.54 (2H, q, J = 7.2Hz), 2.90-3.50 (6H, m) , 3.74-3.89 (ÍH, m), 4.45, 4.7 5 (ÍH, s), 4.86 (2H, s), 6.95 (2H, d, J = 8.5Hz), 7.16-7.20 (1H, m), 7.31-7.35 (HH, m), 7.55 (2H, d, J = 8.5Hz) Example 325 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) - 2- [5- (4- (Cyclopropyl aminocarbonylmethyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (140 mg) NMR (DMSO-d6, d ): 0.45-0.50 (2H, m), 0.60-0.65 (2H, m), 1.35-1.65 (6H, m), 1.70-2.07 (4H, m), 2.35-2.45 (HH, m), 2.65-2.74 (HH, m), 2.90-3.50 (6H, m), 3.75-3.90 (HH, m), 4.47 (2H, s), 4.45, 4.75 (HH, s), 6.98 (2H, d, J = 8.5Hz ), 7.15-7.20 (HH, m), 7.30-7.35 (HH, m), 7.58 (2H, d, J = 8.5Hz), 8.15 (HH, br), 11.20 (HH, s) Example 326 1, 1 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3-hydroxyphenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide dioxide (205) mg) NMR (DMS0-d6, d): 1.35-1.64 (6H, m), 1.66-2.05 (4H, m), 2.35-2.45 (HI, m), 2.90-3.50 (6H, m), 3.75- 3.90 (ÍH, m), 4.45, 4.75 (ÍH, s), 6.70-6.73 (ÍH, m), 7.00-7.07 (2H, m), 7.16-7.21 (2H, m), 7.35- 7.40 (ÍH, m) , 9.61 (ÍH, s) EXAMPLE 327 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (5-acetyl-2-thienyl) -2-thienyl] -3,4,5,6-tetrahydroxy-1,2-dioxide 2H-thiopyran-2-acetamide (100 mg) NMR (CDC13, d): 1.43-1.78 (6H, m), 1.85-1.98 (2H, m), 2.05-2.25 (2H, m), 2.58 (3H, s) ), 2.63-2.86 (2H, 2.95-3.17 (4H, m), 2.95-3.61 (HH, m), 3.65-3.82 (HH, m), 4.51, 4.83 (HH, s), 7.18 (HH, d, J-4.0HZ), 7.57 (HH, d, J = 4.0Hz), 7.64 (HH, d, J = 4.0Hz), 7.70 (HH, d, J = 4.0Hz) Example 328 1,1-dioxide was obtained of (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4-aminocarbonyl phenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (49 mg) ) of (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4-carboxyphenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran 1,1-dioxide -2-acetamide (133 mg) in a manner similar to that of Example 32. NMR (CDC13, d): 1.45 (2H, br), 1.63-1.68 (2H, m), 1.94 (2H, br), 2.08- 2.17 (2H, m), 2.30- 2.36 (2H, m), 3.00-3.22 (4H, m), 3.26-3.47 (HH, m), 3.68-3.76 (HH, m), 4.55 (1 / 2H) , br), 4.85 (1 / 2H, br), 7.43-7.57 (5H, m), 7.63-7.70 (3H,), 7.75-7.80 (HH, m) MS (ESI +): 493.6 (M + H) Example 329 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (benzylaminocarbonyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydroxy-1,1-dioxide was obtained. 2H-thiopyran-2-acetamide (85 mg) in a manner similar to that of Example 328.

NMR (CDCI3, d): 1.51-1.60 (2H, m), 1.70-1.79 (4H, m), 1.89-1.96 (2H, m), 2.08-2.16 (2H, m), 2.76-2.83 (2H, br ), 2.97-3.14 (4H, m), 3.40-3.64 (ÍH, m), 3.72-3.92 (ÍH, m), 4.60- 4.65 (2H, m), 4.68 (1 / 2H, 35 br), 4.84 ( 1 / 2H, br), 7.20-7.37 (7H, m), 7.56-7.83 (4H, m) MS (ESI-): 581.2 (MH) The following compounds were obtained in a manner similar to that of Example 130. Example 330 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (ethoxycarbonylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H- thiopyran-2-acetamide (190 mg) NMR (CDCl 3, d): 1.34 (H, t, J = 7.0 Hz), 1.46 (2 H, br), 1.64-1.69 (4 H, m), 1.94 (2 H, br) , 2.07- 2.20 (2H, m), 2.67-2.68 (2H, m), 3.06 (2-H, s), 3.11-3.16 (2H, m), 3.30-3.48 (H, m), 3.60-3.70 ( ÍH,), 4.23 (2H, q, J = 7.0Hz), 4.53 (1 / 2H, br), 4.81 (1 / 2H, br), 6.69 (ÍH, s), 7.27-7.32 (5H,), 7.64 (ÍH, s), 8.05 (1 / 2H, s), 8.20 (1 / 2H, s) MS (ESI-): 535.2 (MH) Example 331 1, 1-dioxide (2S) -N- (2- tetrahydropyra nyloxy) -2- [5- (3- (n-propoxycarb onyl amino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (170 mg) NMR (CDC13 , d): 0.99 (3H, t, J = 6.0Hz), 1.45 (2H, br), 1.63-1.75 (6H, m), 1.95 (2H, br), 2.06-2.21 (2H, m), 2.63- 2.91 (2H, m), 3.05 (2H, s), 3.12 (2H, br), 3.28-3.50 (HH,), 3.58- 3.69 (HH,), 4.07-4.15 (2H, m), 4.52 (1 / 2H, br), 4.80 (1 / 2H, br), 6.65 (H, s), 7.20-7.30 (5H, m), 7.66 (H, s), 7.96 (1 / 2H, s), 8.12 (1 / 2H, s) MS (ESI-): 549.4 (MH) EXAMPLE 332 1, 1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (isopropoxycarbonylamino) phenyl) -2- thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (160 mg) NMR (CDCl 3, d): 1.31 (6H, d, J = 7.5Hz), 1.45 (2H, br), 1.64-1.68 (4H, m), 1.94 (2H, br), 2.05-2.21 (4H, m), 2.64-2.86 (2H, m), 3.05 (2H, s), 3.10-3.15 (2H, m), 3.30-3.38 (ÍH, m), 3.60-3.70 (ÍH, m), 4.52 (1 / 2H, br), 4.80 (1 / 2H, br), 5.02 (ÍH, qq, J = 7.5, 7.5Hz), 6.59 (ÍH, s), 7.24-7.28 (5H, m), 7.67 (ÍH , s), 7.94 (1 / 2H, s), 8.10 (1 / 2H, s) MS (ESI-): 549.4 (MH) Example 333 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5-. { 3- (2-chloroethoxycarboni lamino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (155 mg) NMR (CDC13, d): 1.45 (2H, br), 1.62-1.68 (4H, m), 1.95 (2H, br), 2.07-2.22 (2H, m), 2.63-2.89 (2H, m), 3.05 (2H, s), 3.10-3.16 (2H, m), 3.28-3.48 (ÍH, m), 3.61-3.66 (ÍH, m), 3.75 (2H, t, J = 5.0Hz), 4.43 (2H, t, J = 5.0Hz), 4.52 (1 / 2H, br), 4.80 (l / 2Hr br), 6.80 (ÍH, s), 7.23-7.31 (5H, m), 7.65 (ÍH, s), 8.02 (1 / 2H, s), 8.17 (1 / 2H, s) MS (ESI-): 569.3 (MH) EXAMPLE 334 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (valeryl phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H -thiopyran-2-acetamide (148 mg) NMR (CDCI3, d): 0.96 (3H, t, J = 7Hz), 1.32-1.78 (12H, m), 1.85-1.99 (2H, m), 2.03-2.25 ( 2H, m), 2.40 (2H, t, J = 7Hz), 2.69-2.93 (2H, m), 2.98-3.18 (2H, m), 3.28-3.51 (ÍH, m), 3.62- 3.77 (ÍH, m ), 4.55, 4.83 (ÍH, s), 7.10-7.32 (4H,), 7.47-7.69 (3H, m), 8.66 (ÍH, s) MS (ESI-): 547 (MH) Example 335 1, 1- (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (ethyl) dioxide thiocarbonylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (130 mg) NMR (CDC13, d): 1.26 (3H, t, J = 8Hz), 1.39 -1.77 (8H, m) 1.34-2.00 (2H, m), 2.06-2.75 (2H, m), 2.71- 2.96 (2H, m), 2.99 (2H, q, J = 8Hz), 3.04-3.17 (2H , m), 3.29-3.52 (2H, m), 3.64-3.76 (HH,), 4.55, 4.84 (HH, s), 7.15-7.32 (4H, m), 7.38-7.54 (3H, m), 8.49, 8.58 (1H, s) MS (ESI-): 551 (MH) EXAMPLE 336 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (methylthiocarbonylamino) phenyl) - 2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (192 mg) NMR (CDCl 3, d): 1.36-1.78 (8H, m), 1.86-2.00 (2H,), 2.07-2.75 (2H, m), 2.43, 2.45 (3H, s), 2.72-2.97 (2H, m), 3.03-3.22 (2H, m), 3.30-3.54 (ÍH, m), 3.64-3.76 (ÍH) , m), 4.56, 4.74 (ÍH, br s), 7.12-7.32 (4H, m), 7.40- 7.53 (2H,), 7.62-7.71 (ÍH, m), 8.65, 8.72- (ÍH, s) MS (ESI-): 537 (MH) EXAMPLE 337 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (benzyloxycarbonyllamino) phenyl) -2 -thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (87 mg) NMR (CDCI3, d): 1.35-1.72 (8H, m), 1.86-1.98 (2H, m ) 2.02-2.21- (2H, m), 2.65-2.92 (2H, m), 2.98-3.16 (2H, m), 3.28-3.50 (HH, m), 3.62-3.73 (HH, m), 4.52, 4.71 (ÍH, s), 5.21 (2H, s), 6.88 (ÍH, br s), 7.19-7.46 (10H, m), 7.62 (ÍH, br s), 8.26, 8.38 (ÍH, s) MS (ESI- ): 597 (MH) EXAMPLE 338 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- (4-chlorofenyl) acetylamino) phenyl) -2- thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (158 mg) NMR (CDCl 3, d): 1.35-1.79 (5H, m), 1.87-1.99 (2H, m), 2.04 -2.24 (2H,), 2.17-2.93 (HH, m), 3.02-3.17 (2H, m), 3.27-3.52 (HH, m), 3.63-3.74 (1H, m), 4.53, 4.82 (H, s) ), 4.59 (2H, s), 6.83 (HH, d, J = 8Hz), 6.96 (2H, d, J = 8Hz), 7.22-7.39 (5H, m), 7.56-7.614 (HH, m), 7.22 -7.28 (ÍH, m), 8.30 (HH, s), 8.34, 8.45 (HH, s) MS (ESI +): 633, 634 (M + H) Example 339 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (phenoxycarbonylamino) phenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (124 mg) NMR (CDC13, d): 1.34 (8H, m ), 1.85-1.99 (2H, m), 2.03-2.24 (2H, m), 2.68-2.94 (2H, m), 3.00-320 (2H, m), 3.29-3.53 (HI, m), 3.62-3.77 (ÍH, m), 4.53, 4.82 (ÍH, s), 7.11-7.47 (11H, m), 7.63, 7.67 (ÍH, s), 8.49, 8.57 (ÍH, s) MS (ESI-): 583 (MH Example 340 1, (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- (4-morpholinocarbonylamino) acetylamino) phenyl) -2-thienyl] -3,4-dioxide , 5,6-tetrahydro-2H-thiopyran-2-acetamide (85 mg) NMR (DMSO-d6, d), 1.32-2.09 (10H, m), 2.34-2.51 (H, m), 2.87-3.62 (14H , m), 3.73-3.92 (ÍH, m), 3.80 (2H, d, J = 7Hz), 4.43, 4.76 (ÍH, s), 6.96 (ÍH, t, J = 7Hz), 7.17-7.26 (ÍH, m), 7.32-7.53 (4H, m), 8.02 (H, s) MS (ESI-): 633 (MH) Example 341 (2S) -N- (2-tetrahydropyranyloxy) -2- [ 5- (3- (2- (N-ethyl- N -methylaminocarbonyloxy) acetylamino) phenyl) -2-thienyl] -5 3,4,5,6-tetrahicyl-2H-thiopyran-2-acetamide 1,1-dioxide (220 mg) was obtained in a manner similar to that of Example 211. NMR (CDC13, d): 1.18, 1.23 (3H, t, J = 8Hz), 1.37- 1.74 (8H, m), 1.89-2.01 (2H, m), 2.06-2.23 (2H, m), 2.72-2.88 (2H, m), 2.99, 3.03 (3H, s), 3.05-3.18 (2H, m), 3.15-3.28 (HH, m), 4.53, 4.83 (HH, s), 4.72, 4.74 (2H, s) , 7.15-7.32 (4H, m), 7.52 (HH, brs), 7.59, 7.64 (HH, brs), 8.23 (HH, s), 8.62-8.75 (HH, m) MS (ESI-): 606 (MH) The following compounds were obtained in a manner similar to that of Example 129. EXAMPLE 342 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (benzylaminocarbonyl) lamino ) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (80 mg) NMR (CDC13, d): 1.42 (2H, br), 1.60-1.66 (4H, m), 1.83-1.90 (2H, m), 2.00-2.18 (2H, m), 2.74 (2H, br), 2.92-3.00 (2H, m), 3.04-3.10 (2H,), 3.30-3.50 (ÍH) , m), 3.68-3.78 (ÍH, m), 4.33-4.42 (2H, m), 4.57 (1 / 2H, br), 4.72 (1 / 2H, br), 6.93-7.12 (6H, m), 7.27 -7.25 (2H, m), 7.28-7.32 (4H, m) MS (ESI-): 596.4 (MH) Example 343 1, 1-dioxide (2S) -N- (2-tetrah idropyranyloxy) -2- [5- (3- (4-methoxyphenylaminocarbonylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (224 mg) NMR (CDCl 3, d): 1.43 (2H, br), 1.62-1.73 (4H, m), 1.90 (2H, br), 2.03-2.20 (2H,), 2.77 (2H, br), 2.96-3.03 (2H, m) ), 3.08-3.14 (2H, m), 3.33-3.54 (HH, m), 3.68-3.75 (HH, m), 3.77 (3H, s), 4.61 (1 / 2H, br), 4.86 (1 / 2H) , br), 6.80-6.93 (4H, m), 7.10-7.29 (6H, m), 7.38-7.53 (4H,), 9.04 (1 / 2H, s), 9.42 (1 / 2H, s) MS (ESI -): 611.5 (MH) EXAMPLE 344 (2-S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (ethoxy-carbonylmethylaminocarbonylamino) phenyl) -2-thienyl 1,1-dioxide] - 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (490 mg) NMR (CDC13, d): 1.22-1.33 (5H, m), 1.42-1.47 (2H, m), 1.62-1.70 (2H, m), 1.94 (2H, br), 2.07-2.20 (2H, m), 2.74-2.86 (2H, m), 3.08- 3.20 (2H,), 3.49-3.52 (2H, m), 3.68-3.78 (2H, m), 3.97-4.27 (4H, m), 4.58 (1 / 2H, br), 4.85 (1 / 2H, br), 5.68-5.80 (HH, m), 6.96-2.24 (5H,), 7.28-7.34 (HH, m), 7.40-7.46 (HH, m), 9.12 (1 / 2H, s), 9.31 (1 / 2H, s) MS (ESI-): 592.3 (MH) EXAMPLE 345 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- ( 3- (ut i lami noc a rbon i 1 ami thio) phenyl) -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (330 mg) NMR (CDCI3, d): 0.90 (3H, dd, J = 7.2, 7.2Hz), 1.26-1.74 (10H, m), 1.85-1.99 (2H, m), 2.02-2.21 (2H, m), 2.74-2.89 (2H, m), 2.97-3.26 (6H, m), 3.31-3.54 (ÍH, m), 3.71-3.80 (ÍH, m), 4.60, 4.83 (ÍH, s), 5.42-5.53 (ÍH, m), 6.95 (ÍH, d , J = 4Hz), 7.01-7.30 (5H, m), 7.38-7.43 (HH, m), 9.3, 9.51 (HH, s) Example 346 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) ) -2- [5- (3- (l-naphthylaminocarbonyl) amino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (350 mg) NMR (CDC13, d): 1.30-1.65 (6H, m), 1.75-1.92 (2H, m), 1.93-2.19 (2H, m), 2.70-2.88 (2H, m), 2.92-3.20 (4H, m), 3.30-3.46 (HH, m), 3.70 (HH, br), 4.56 , 4.83 (HH, s), 6.93-7.80 (12H, m), 7.95 (HH, dd, J = 8.0, 8.0Hz) Example 347 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) - 2- [5- (3- (al-laminocarbonyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (300 mg) NMR (CDC13, d): 1.35-1.70 (6H, m), 1.85-2.25 (4H,), 2.75-2.88 (2H, m), 2.95-3.17 (4H, m), 3.30-3.52 (ÍH, m), 3.70-3.90 (3H, m), 4.59, 4.83 (ÍH, s), 5.10-5.23 (2H,), 5.40- 5.49 (ÍH, m), 5.80-5.94 (ÍH, m), 6.95-7.28 (6H, m) MS (ESI- ): 546 (MH) EXAMPLE 348 To a solution of (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3-aminophenyl) -2-thienyl] -3,4-dioxide, 5,6-tetrahydro-2H-thiopra-2-acetamide (150 mg) and thienylamine (163 mg) in N, N-dimethylformamide (3 ml) was added 3- ( phenoxycarbonylamino) pyridine (83 mg) and the reaction mixture was stirred at room temperature for 14 hours. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel 60 (eluent: 3% methanol chloroform) to form 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (3-pyridylaminocarbonylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (150 mg) as a white amorphous. NMR (CDC13, d): 1.38 (2H, br), 1.45-1.62 (4H, m), 1.94 (4H, br), 2.05-2.25 (2H, m), 2.92 (2H, br), 3.02-3.11 ( 4H, m), 3.32-3.50 (ÍH,), 3.78 (1H, br), 4.20-4.23 (ÍH, m), 4.62 (1 / 2H, br), 4.94 (1 / 2H, br), 6.89-7.27 (4H,), 7.30-7.46 (HH, m), 7.51-7.72 (2H, m), 8.03-8.21 (HH, m), 8.40 (1 / 2H, s), 8.45 (1 / 2H, s) MS (ESI +): 585.4 (M + H) The following compounds were obtained in a manner similar to that of Example 130. EXAMPLE 349 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (allyloxycarbonylamino) phenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (160 mg) NMR (CDC13, d): 1.45 (2H, br), 1.58 -1.68 (4H, m), 1.94 (2H, br), 2.07-2.22 (2H, m), 2.66- 2.90 (2H,), 3.04-3.52 (2H, m), 3.09-3.15 (HI, m), 3.30-3.49 (ÍH, m), 3.63-3.72 (ÍH, m), 4.52 (1 / 2H, br), 4.67 (2H, d, J = 7.0Hz), 4.80 (1 / 2H, br), 5.27 ( HH, d, J = 8.0Hz), 5.38 (HH, d, J = 8.0Hz), 5.89-6.04 (HH, m), 6.83 (HH, s), 7.24-7.34 (5H, m), 7.63 (HH) , s), 8.20 (1 / 2H, s), 8.35 (1 / 2H, s) MS (ESI-): 547.3 (MH) Example 350 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [ 5- (3- (2-benzyloxy-acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (410 mg) NMR (CDCl 3, d): 1.45 (2H) , br), 1.61-1.68 (4H, m), 1.95 (2H, br), 2.06-2.22 (2H, m), 2.64- 2.87 (2H, m), 3.03 (2H, br s), 3.08-3.13 ( 2H, m), 3.28-3.47 (HH, m), 3.61-3.67 (HH, m), 4.08 (2H, d, J = 7.5Hz), 4.52 (1 / 2H, br), 4.63 (HH, s) , 4.68 (ÍH, s), 4.67 (2H, d, J = 15Hz), 4.82 (1 / 2H, br), 7.30-7.40 (9H, m), 7.53 (ÍH, d, J = 5.0Hz), 7.77 (HH, s), 8.01 (HH, s), 8.16 (HH, s), 8.34 (HH, s) MS (ESI-): 611.5 (MH) The following compounds were obtained in a manner similar to that of Example 211. Example 351 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5-. { 3- (((2S) -2- (tert-butoxycarbonylamino) propionyl) amino) phenyl} -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (310 mg) NMR (CDC13, d): 1.43-1.48 (HH,), 1.65-1.68 (4H, m), 1.94 (42H, br), 2.04-2.20 (2H, m), 2.67-2.87 (2H, m), 3.04-3.07 (2H, m), 3.10- 3.15 (2H, m), 3.28-3.62 (HH, m), 3.63-3.75 (HH, m), 4.32 (HH, br), 4.52 (1 / 2H, br), 4.82 (1 / 2H, br), 7.20-7.30 (4H, m), 7.40-7.50 (HI, m), 7.67 (1 / 2H, s), 7.77 (1 / 2H, s), 8.36 (1 / 2H, s), 8.54 (1 / 2H, s) MS (ESI-): 634.3 (MH) Example 352 1, 1-dioxide (2S) -N- (2-tetrahydropylalyloxy) -2- [ 5- . { 3- (((2R) -2- (ter-but oxycarbonylamino) propionyl) amino) phenyl} -2-thienyl) -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (475 mg) NMR (CDC13, d): 1.43-1.48 (14H, m), 1.65-1.68 (4H, m ), 1.94 (42-H, br), 2.04-2.20 (2H, m), 2.67-2.87 (2H, m), 3.04-3.07 (2H, m), 3.10- 3.15 (2H, m), 3.28-3.62 (ÍH, m), 3.63-3.75 (ÍH, m), 4.32 (ÍH, br), 4.52 (1 / 2H, br), 4.82 (1 / 2H, br), 7.20-7.30 (4H, m), 7.40 - 7.50 (ÍH, m), 7.67 (1 / 2H, s), 7.77 (1 / 2H, s), 8.36 (1 / 2H, s), 8.54 (1 / 2H, s) MS (ESI-): 634.3 (MH) EXAMPLE 353 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5-. { 3- (2- (4-methylfenoxy) acetylamino) phenyl} -2-thiyl enyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (230 mg) NMR (CDCl 3, d): 1.44 (2H, br), 1.56-1.68 (4H, m) , 1.95 (2H, br), 2.07-2.21 (2H, m), 2.33 (3H, s), 2.63-2.90 (2H,), 3.05 (2H, s), 3.11-3.13 (2H, br), 3.30- 3.48 (ÍH, m), 3.60- 3.70 (ÍH, m), 4.52 (1 / 2H, br), 4.60 (2H, s), 4.80 (1 / 2H, br), 6.90 (2H, d, J = 8.0 Hz), 7.15 (2H, d, J = 8.0Hz), 7.22-7.29 (2H, m), 7.33- 7.36 (2H, m), 7.55-7.59 (HH, m), 7.80 (HH, s), 8.00 (1 / 2H, s), 8.14 (1 / 2H, s), 8.32 (HH, s) MS (ESI-): 611.3 (MH) Example 354 1, 1-dioxide (2S) -N- (2- tetrahydropyranyloxy) -2- [5-. { 3- (2- (N, N-dimethylamino) acetylamino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (90 mg) NMR (CDC13, d): 1.46 (2H, br), 1.62-1.68 (4H, m), 1.95 (4H, br), 2.04-2.23 (2H, m), 2.41 (6H, s), 2.65-2.88 (HI, m), 3.05 (2H, s), 3.10 (2H,), 3.12-3.15 (2H , m), 3.26-3.49 (ÍH, m), 3.62-3.72 (ÍH, m), 4.52 (1 / 2H, br), 4.80 (1 / 2H, br), 7.23-7.29 (2H, m), 7.34 (2H, d, J = 5.0Hz), 7.60-7.66 (HH, m), 7.76 (HH, br), 8.00 (1 / 2H, br), 6.18 (1 / 2H, br), 9.19 (HH, s) ) MS (ESI +): 550.3 (M + H) Example 355 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- (4-chloro-phenyl) -acetylamino) ) phenyl) -2-thiyl enyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (158 mg) NMR (CDC13, d): 1.34-1.98 (10H, m), 2.03-2.25 (2H, m), 2.69-22.88 (2H, m), 3.02-3.18 (2H, m), 3.27-3.51 (HH, m), 3.62-3.26 (HH, m), 3.68 (2H, s), 4.53 , 4.83 (ÍH, br s), 7.00- 7.66 (10H, m), 7.73, 7.76 (ÍH, s), 8.65-8.75 (ÍH, m) MS (ESI-): 616 (MH) Example 356 1, 1 - (2S) -N- (2-tetrahydropyranyloxy) dioxide ) -2- [5- (3- (((R) -2-tert-butoxycarbonylamino-2-phenylacetyl) amino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran- 2-acetamide (117 mg) NMR (DMSO-ds, d): 1.20-1.62 (6H, m), 1.40 (9H, s), 1.68-2.06 (4H, m), 2.34-2.48 (H, m), 2.86-3.32 (5H, m), 3.73-3.86 (ÍH,), 4.40, 4.75 (ÍH, br s), 5.86 (ÍH, d, J = 8Hz), 7.16- 7.23 (ÍH, m), 7.28-7.61 (10H, m), 7.96 (HH, s), 10.37 (HH, s), 11.23 (HH, s) MS (ESI-): 696 (MH) Example 357 (2S) -N- 1,1-dioxide (2-tetrahydropyranyloxy) -2- [5- (3- (2-isopropoxy acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (276 mg) NMR (CDC13, d): 1.29 (6H, d, J = 7Hz), 1.36-1.77 (8H, m), 1.88-2.00 (2H, m), 2.65-2.92 (2H, m), 3.02-3.18 (2H , m), 3.28-3.51 (ÍH, m), 3.62-3.73 (ÍH, m), 3.77 (ÍH, q, J = 7Hz), 4.07 (ÍH, s), 4.52, 4.82 (ÍH, br s), 7.23-7.48 (4H, m), 7.52-7.60 (ÍH,), 7.78 (ÍH, s), 8.18, 8.32 (ÍH, br s), 8.40 (ÍH, s) MS (ESI +): 565 (M + H Example 358 1, 1-diox gone from (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- ((l-tert-butoxycarbonyl-4-piperidinyloxy) acetylamino) phenyl) -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (360 mg) NMR (CDC13, d): 1.40-1.77 (10H, m), 1.47 (9H, s), 1.89-2.01 (4H, m), 2.06-2.24 (2H, m), 2.68-2.92 (2H, m), 3.02-3.18 (4H, m), 3.28- 3.52 (HH, m), (2H, m), 3.79-3.92 (2H, m), 4.12 (2H,), 4.53, 4.82 (H, s), 7.22-7.38 (4H, m), 7.52-7.58 (H, m), 7.76 (H, s), 8.27, 8.84 (H, s), 8.34 , 8.38 (OH, s) MS (ESI +): 706 (M + H) Example 359 1.1-(2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- ( 2-oxo-l, 3-oxazolidin-3-yl) acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (600 mg) NMR (DMSO-d6, d): 1.36-1.64 (6H, m), 1.69-2.06 (4H, m), 2.34-2.48 (HH, m), 2.88-3.32 (5H, m), 3.42-3.53 (HH) , m), 3.66 (2H, t, J = 8Hz), 3.73-3.90 (ÍH, m), 4.34 (2H, t, J = 8Hz), 4.44, 4.75 (ÍH, s), 7.17-7.25 (ÍH, m), 7.33-7.48 (4H, m), 8.03 (OH, s) MS (ESI-): 590 (MH) Example 360 To a suspension of (2S) -N- (2-tetrahydropyranyloxy) 1,1-dioxide ) -2- [5- (3-aminophenyl) -2-thienyl] -3,, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (300 mg) and triethylamine (392 mg) in chloroform (4 ml) triphosgene (192 mg) was added at 0 ° C and the reaction mixture was stirred at room temperature for 30 minutes. To the mixture was added (2- ((tert-butyl) (diphenyl) silyloxy) ethyl) amine (232 mg) at 0 ° C and the reaction mixture was stirred at room temperature for 2 hours. The mixture was poured into water and extracted with chloroform. The organic layer was washed with water, a solution of 10% citric acid, saturated aqueous sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel 60 (eluent: 2% methanol chloroform) to form 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- ((tert-butyl) (diphenyl) silyloxy) ethylaminocarbonyl-amino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (350 mg) as an amorphous White. NMR (CDC13, d): 1.04 (9H, s), 1.44 (2H, br), 1.62-1.68 (4H, m), 1.85-1.94 (2H, br), 2.05-2.19 (2H, m), 2.69- 2.90 (2H, m), 2.98-3.10 (4H,), 3.31-3.44 (3H, m), 3.62-3.80 (3H, m), 4.56 (1 / 2H, br), 4.80 (1 / 2H, br) , 6.64 (ÍH, s), 7.09-7.30 (5H, m), 7.32-7.42- (7H, m), 7.56-7.64 (4H, m), 8.62 (ÍH, s) MS (ESI-): 788.5 ( MH) The following compounds were obtained in a manner similar to that of Example 130. EXAMPLE 361 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (cyclopentylcarbonyl amine)) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (205 mg) NMR (CDC13, d): 1.46 (2H, br), 1.60-1.70 (6H) , 1.77-1.84 (2H, ra), 1.91-1.97 (6H, m), 2.07-2.21 (2H, m), 2.66-2.89 (2H, m), 2.71 (ÍH, tt, J = 7.5, 7.5Hz) , 3.05 (ÍH, s), 3.10- 3.15 (2H, m), 3.30-3.49 (ÍH, m), 3.63-3.70 (ÍH, m), 4.54 (1 / 2H, br), 4.82 (1 / 2H, br), 7.20-7.30 (4H, m), 7.41 (2H, br), 7.52 (ÍH, br), 7.71 (ÍH, br), 8.25 (1 / 2H, s), 8.37 (1 / 2H, s) MS (ESI-): 559.4 (MH) EXAMPLE 362 1 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (3-chloropropionylamino) phenyl) -2-thienyl] -1-dioxide] - 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (145 mg) NMR (CDCl 3, d): 1.45 (2H, br), 1.54-1.72 (4H, m), 1.95 (4H, br) , 2.09-2.24 (2H, m), 2.72- 2.82 (2H, m), 2.85 (2H, t, J = 6.4Hz), 3.00- 3.08 (2H, m), 3.11-3.16 (2H, m), 3.29 -3.52 (ÍH, m), 3.63-3.73 (ÍH, m), 3.91 (2H, t, J = 6.5Hz), 4.54 (1 / 2H, br), 4.63 (1 / 2H, br), 7.15-7.30 (4H, m), 7.54-7.72 (3H, m), 8.50 (HH, s) MS (ESI-): 553.3 (MH) The following compounds were obtained in a manner similar to that of Example 360. Example 363 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (isobutylaminocarbonylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2 -acetaptide (230 mg) NMR (CDC13, d): 0.90 (6H, d, J = 6.6Hz), 1.40-1.70 (7H, m), 1.88-1.97 (2H, m), 2 .65-2.22 (2H , m), 2.99-3.18 (6H, m), 3.31-3.51 (ÍH, m), 6.96-7.29 (6H, m), 7.47-7.53 ( H, m), 9.25, 9.47 (HH, s) MS (ESI-): 562 (MH) Example 364 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3 - (cyclohexylmethylaminocarbonylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopra-ran-2-acetamide (200 mg) NMR (CDCl 3, d): 0.83-1.00 (2H, m) , 1.10-1.25 (4H, m), 1.35-1.54 (5H,), 1.55-1.79 (6H, m), 1.85-1.98 (2H, m), 2.01-2.22 (2H, m), 2.75-2.89 (2H ,), (2H, m), 3.00-3.22 (6H, m), 3.30-3.52 (ÍH, m), 3.66-3.82 (ÍH, m), 1.59, 4.84 (ÍH, s), 5.45-5.55 (ÍH) , m), 6.95-7.30 (6H, m), 7.40 (1H, br) Example 365 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2 - methoxy et i 1 aminocarbonyl amino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopra-ran-2-acetamide (220 mg) NMR (CDC13, d): 1.38-1.68 (6H , m), 1.85-1.98 (2H, m), 2.03-2.18 (2H, m), 2.75-2.90 (2H, m), 3.01-3.17 (4H, m), 3.30-3.35 (H, m), 3.38 (3H, s), 3.42-3.55 (4H, m), 3.66-3.77 (HH, m), 4.55, 4.84 (HH, s), 5.51-5.60 (HH, m), 7.05-7.40 (6H, m ), 9.10, 9.20 (ÍH, s) MS (ESI-): 564 (MH) EXAMPLE 366 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- ((N-methyl-N-ethylaminocarbonyl) amino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopra-ran-2-acetamide (200 mg) NMR (CDCl 3, d): 1.33 (3H, t, J = 7.0Hz), 1.40-1.75 (6H, m), 1.85-1.98 (2H, m), 2.05-2.20 (2H, m), 2.60-2.90 (4H, m), 3.00-3.20- (5H, m), 3.29- 3.50 (HH, m), 3.62-3.73 (HH, m), 4.23 (2H, J = 7.0Hz), 4.53, 4.80 (HH, s), 7.15-7.35 (6H, m) MS (ESI-): 548 (MH) EXAMPLE 367 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- ((2-phthalimidoethoxy) carbonylamino) phenyl) -2-thienyl] -3,4 , 5,6-tetrahydro-2H-thiopyran-2-acetamide (155 mg) of (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3-amino-phenyl) -2-dioxide -thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (300 mg) and 2-f taloylethanol NMR (CDC13, d): 1.42-1.70 (6H,), 1.81-1.96 (2H , m), 2.02-2.23 (2H, m), 2.97-3.27 (4H, m), 3.49 (2H, br), 3.52-3.75 (2H, m), 4.04 (2H, br), 4.16-4.48 (H) , ), 5.05-5.23 (HH,), 6.76-7.36 (8H, m), 7.66-7.74 (2H,), 7.79-7.87 (2H, m) MS (ESI-): 680.5 (MH) The following compounds were obtained in a manner similar to that of Example 32. Example 368 1 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (2-phenylaminocarbonyletenyl) phenyl) -2-thienyl] - dioxide] - 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (100 mg) NMR (DMSO-d6, d): 1.38-1.62 (6H, m), 1.72-2.06 (4H, m), 2.38- 2.47 (ÍH, m), 2.90-3.52 (6H, m), 3.75-3.90 (ÍH, m), 4.45, 4.75 (ÍH, s), 6.86 (ÍH, d, J = 16Hz), 7.06 (ÍH, dd , J = 8.0, 8.0Hz), 7.24-7.27 (2H, m), 7.34 (2H, d, J = 8.0, 8.0Hz), 7.55-7.58 (2H, m), 7.65-7.76 (6H, m) Example 369 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (2- (4-methoxy-phenylaminocarbonyl) ethenyl) phenyl) -2-thienyl] -3,4-dioxide , 5,6-tetrahydro-2H-thiophen-2-acetamide (150 mg) NMR (DMSO-ds, d): 1.37-1.64 (6H, m), 1.71-2.08 (4H, m), 2.36-2.47 (ÍH, m), 2.90-3.51 (6H, m), 3.74 (3H, s), 3.75-3.90 (ÍH, m), 4.45, 4.75 (ÍH, s), 6.82 (ÍH, d, J = 6Hz), 6.92 (2H, d, J = 8.5Hz), 7.24-7.27 (ÍH, m), 7.54-7.75 (8H, m) Example 370 1 , (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (2- (4-f luorofenyl aminocarbonyl) ethenyl) phenyl) -2-thienyl] -3,4-dioxide, 5,6-tetrahydro-2H-thiopyran-2-acetamide (150 mg) NMR (DMSO-dg, d): 1.37-1.62 (6H, m), 1.70-2.08 (4H, m), 2.36-2.46 (1H, m), 2.91-3.54 (6H, m), 3.75-3.90 (HH, m), 4.45, 4.75 (HH, s), 6.83 (HH, d, J = 16Hz), 7.18 (2H, dd, J = 8.5 , 8.5Hz), 7.24-7.27 (HH, m), 7.55-7.75 (8H, m), 10.3 (HH, s) Example 371 1, 1-dioxide (2S) -N- (2-tetrahydropranyloxy) -2- [5- (4- (2- (N, N-dimethylaminocarbonyl) ethenyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopra-ran-2-acetamide (250 mg) NMR (CDC13, d): 1.35-1.75 (6H, m), 1.88-2.01 (2H, m), 2.05-2.25 (2H,), 2.65-3.18 (9H, m), 3.20 (3H, s) , 3.26-3.49 (HH, m), 3.64- 3.70 (HH, m), 4.54, 4.83 (HH, s), 6.91 (HH, d, J = 16Hz), 7.29 (HH, d, J = 4.0Hz) , 7.47- 7.69 (6H,) Example 372 1 (1S) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (2- (isopropylaminocarbonyl) ethenyl) f-enyl) -2-thienyl] -3,4,5, 6-tetrahydro-2H-thiopra-ran-2-acetamide (220 mg) NMR (DMSO-d6, d): 1.11 (6H, d, J = 5Hz), 1.37-1.64 (6H,), 1.70-2.07 (4H ,), 2.35-2.46 (HH, m), 2.90-3.37 (5H, m), 3.40-3.54 (2H, m), 3.74-3.90 (1H, m), 3.90-4.01 (HH, m), 4.45, 4.75 (ÍH, s), 6.62 (ÍH, d, J = 16Hz), 7.21- 7.25 (ÍH, m), 7.40 (ÍH, d, J = 16Hz), 7.51- 7.55 (ÍH, m), 7.57 (2H , d, J = 8.5Hz), 7.69 (2H, d, J = 8.5Hz), 7.99 (ÍH, d, J = 7.5Hz) EXAMPLE 373 1 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (2- (propylaminocarbonyl) ethenyl) phenyl) -2-thienyl] -3,4,5-dioxide 6-tetrahydro-2H-thiopyran-2-acetamide (210 mg) ^^^^^ NMR (DMSO-d6, d): 0.88 (3H, t, J = 7.5Hz), 1.36-1.62 (8H, m), 1.70-2.06 (4H, m), 2.35-2.45 (ÍH, m), 2.40-3.30 (7H, m), 3.41-3.52 (2H, m), 3.74-3.90 (HH, m), 4.45, 4.75 (HH, s), 6.65 (HH, d, J = 16Hz), 7.22-7.25 (HH, m), 7.40 (HH, d, J = 16Hz), 7.51-7.55 (HH, m), 7.60 (2H, d, J = 8.5Hz), 7.70 (2H), d, J = 8.5Hz), 8.10 (H, t, J = 7.0Hz), 11.2 (H, s) Example 374 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [ 5- (4- (n-propylaminocarbonylmethoxy) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (240 mg) NMR (DMS0-d6, d): 0.8 ( 3H, t, J = 7.5Hz), 1.36- 1.63 (8H,), 1.70-2.05 (4H, m), 2.33-2.44 (ÍH, m), 2.93-3.50 (8H, m), 3.74-3.91 (ÍH , m), 4.45, 4.75 (ÍH, s), 4.50 (2H, s), 7.01 (2H, d, J = 8.5Hz), 7.16-7.20 (ÍH, m), 7.33- 7.37 (ÍH, m), 7.58 (2H, d, J = 8.5Hz), 8.10 (OH, br) Example 375 To a suspension of (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- ((2-phthalimidoethoxy) carbonylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (155 mg) in methanol (4 ml) was added hydrazine monohydrate (13.7 mg) and the reaction mixture was stirred at room temperature for 3 hours, the resulting mixture was filtered and washed with methanol. The filtrate was concentrated in vacuo to give (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2-aminoethylaminocarbonylamino) phenyl) -2-thienyl 1,1-dioxide] -3,4 , 5,6-tetrahydro-2H-thiopyran-2-acetamide (125 mg) as a white amorphous. NMR (CDC13, d): 1.24-1.35 (2H, m), 1.42-1.52 (2H, m), 1.62-1.73 (2H, m), 1.96 (2H, br), 2.08-2.25 (2H, m), 2.86 (2H, br), 3.01-3.05 (2H, m), 3.15 (2H, br), 3.44-3.50 (4H,), 3.74-3.84 (HH, m), 4.22-4.25 (HH, m), 4.45 (1 / 2H, br), 4.83 (1 / 2H, br), 7.22-7.30 (4H, m), 7.37-7.44 (HI, m), 7.68 (2H, br, s), 7.83-7.66 (ÍH, m), 8.20-8.24 (HH, m) MS (ESI +): 552.3 (M + H) The following compounds were obtained in a manner similar to that of Example 130. Example 376 1, 1-dioxide (2S) -N - (2-tetrahydropyranyloxy) -2- [5- (4- (ethylcarbonyloxy) phenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (150 mg) NMR (DMSO -ds, d): 1.15 (3H, dd, J = 7.5, 7.5Hz), 1.38-1.61 (6H, m), 1.70-2.07 (4H, m), 2.37- 2.46 (HI, m), 2.58-2.66 (2H, m), 2.90-3.51 (6H, m), 3.75-3.88 (HH, m), 4.43, 4.75 (HH, s), 7.18-7.25 (3H, m), 7.43-7.48 (HH, m) , 7.68 (2H, d, J = 8.5Hz) MS (ESI-): 520 (MH) Example 377 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5 - (4- (me tox i ace toxi) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (150 mg) NMR (DMS0-d6, d): 1.36 -1.62 (6H, m), 1.69-2.05 (4H, m), 2.34-2.43 (HH, m), 2.81-3.29 (5H, m), 3.38 (3H, s) 3.40-3.51 (HH, m ), 3.75- 3.90 (HH, m), 4.37 (2H, s), 4.44, 4.75 (HH, s), 7.20-7.26 (3H, m), 7.42-7.48 (HH, m), 7.70 (2H, d) , J = 8.5Hz) MS (ESI-): 536 (MH) 5 Example 378 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (ethoxycarbonyloxifem) phenyl) -2-thienyl] -3, 4, 5, 6 - ^^ tetrahydro-2H-thiopyran-2-acetamide (150 mg) NMR (DMSO-ds, d): 1.30 (3H, dd, J = 7.5, 7.5Hz ), 0 1.38-1.65 (6H, m), 1.70-1.95 (4H, m), 2.36- 2.45 (ÍH, m), 2.90-3.51 (6H, m), 3.72-3.90 (ÍH, m), 4.27 ( 2H, ddd, J = 7.5, 7.5, 7.5Hz), 7.43, 4.75 (H, s), 7.20-7.26 (H, m), 7.29 (2H, d, J = 8.5Hz), 7.45-7.49 (H, m), 7.69 5 (2H, d, J = 8.5Hz) mMmUMM & < RTI ID = 0.0 > ESTIM < J < / RTI > MS (ESI-): 536 (MH) The following compounds were obtained in a manner similar to that of Example 129. Example 379 1, 1-dioxide (2S ) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (methylaminocarbonyloxy) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (250 mg) NMR (DMSO-ds, d): 1.37-1.62- (4H, m), 1.70-2.05 (4H, m), 2.35-2.46 (HH,), 2.67 (3H, d, J = 4.5Hz), 2.90-3.30 (5H, m), 3.40-3.55 (HH, m), 3.15-3.88 (1H, m), 4.44, 4.75 (HH, s), 7.15 (2H, d, J = 8.7Hz), 7.15- 7.24 (HH, m), 740-7.45 (HH, m), 7.63 (2H, d, J = 8.7Hz) MS (ESI-): 521 (MH) Example 380 1, 1-dioxide (2S) -N - (2-tetrahydropyranyloxy) -2- [5- (4- (ethylaminocarbonyloxy) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (230 mg) NMR (CDC13 , d): 1.23 (3H, dd, J = 7.2, 7.2Hz), 1.36-1.75 (6H, m), 1.66-2.00 (2H,), 2.03- 2.25 (2H, m), 2.65-2.87 (2H, ), 3.01-3.18 (4H, m), 3.26-3.37 (2H, m), 3.60-3.69 (HH, m), 4.51, 4.80 (ÍH, s), 5.01-5.09 (ÍH, m), 7.14 (2H, d, J = 8.7Hz), 7.16-7.25 (2H, m), 7.54 (2H, d, J = 8.7Hz), 8.09 , 8.24 (OH, s) MS (ESI-): 535 (MH) EXAMPLE 381 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4-hydroxyphenyl) - 1,1-dioxide was obtained 2-thienyl] -3,4,5,5,6-tetrahydro-2H-thiopyran-2-acetamide (1 g) in a manner similar to that of Example 201. NMR (CDC13, d): 1.38-1.66 (6H,), 1.70-2.04 (4H, m), 1.84-1.94 (HH, m), 2.69-3.48 (6H,), 3.75-3.90 (HH, m), 4.45, 4.75 (HH, s), 8.80 (2H, d, J = 8.7Hz), 7.13-7.17 (HH, m), 7.21-7.25 (HH, m), 7.45 (2H, d, J = 8.7Hz), 9.68 (HH, s) The following compounds were obtained in a manner similar to that of Example 201. Example 382 1 (1S) -N- (2-tetrahydropyranyloxy) -2- [5- (6-met i 1-3 -pyridyl) -2-thienyl] -3-dioxide , 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (99 mg) NMR (CDCI3, d): 1.40-1.15 (6H, m), 1.90-2.00 (2H, m), 2.01-2.25 (2H , m), 2.59 (3H, s), 2.70-2.94 (2H, m), 3.05-3.17 (4H,), 3.30- 3.52 (ÍH, m), 3. 63-3.74 (ÍH,), 4.52 (0.5H, s), 4.81 (0.5H, s), 7.17 (2H, d, J = 8Hz), 7.26-7.33 (2H, m), 7.75 (ÍH, dd, J = 1.5, 8Hz), 8.12 (0.5H, s), 8.24 (0.5H, s), 8.74 ^^ (ÍH, d, J = 1.5Hz) MS (ESI-): 463 (MH) Example 383 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (6-) 1,1-dioxide methyl-3-pyridyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (110 mg) NMR (CDC13, d): 1.40-1.74 (6H, m), 1.88 -2.00 (2H, m), 2.07-2.20 (2H, m), 2.67-2.87 (2H, m), 3.04-3.08 (2H, m), 3.09-3.18 (2H, m), 3.30-3.52 (ÍH, m), 3.60-3.73 (ÍH, m), 3.96 (3H, s), 4.53 (0.5H, s), 4.81 (0.5H, s), 6.77 (ÍH, d, J = 8Hz), 6.63 (ÍH, d, J = 8Hz), 7.16-7.20 (HH, m), 7.64-7.79 (HH, m), 7.99 (0.5H, s), 8.13 (0.5H, s), 8.39-8.42 (HH, m) MS (ESI-): 479 (MH) The following compounds were obtained in a manner similar to that of Example 130. EXAMPLE 384 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5-. { 3- (2-acetylamino) phenyl} -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (105 mg) NMR (CDCl 3, d): 1.33-1.77 (8H, m), 1.87-2.00 (2H, m ), 2.11 (3H, m), 2.06-2.73 (ÍH, m), 2.85-3.36 (5H,), 3.66-3.93 (2H, m), 4.36- 4.48 (ÍH, m), 4.53 (1 / 2H, br), 4.88 (1 / 2H, br), 7.12-7 .31 (5H, m), 7.59-7.6.7 (HH, m), 8.82 (1 / 2H, br s), 8.84 (1 / 2H, br s), 9.83 (HH, s), 10.04 (HH, s) MS (ESI-): 563.0 (MH) Example 385 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [ 5-. { 3- (3- (methoxycarbonyl) propionylamino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (130 mg) NMR (CDC13, d): 1.44 (4H, br), 1.65-1.67 (2H, m), 1.95 (2H, br), 2.08-2.21 (2H, m), 2.67- 2.77 (6H, m), 3.08-3.14 (4H,), 3.29-3.48 (HH, m), 3.62-3.70 (HH, m) , 3.72 (3H, s), 4.53 (1 / 2H, br), 4.81 (1 / 2H, br), 7.20-7.27 (3H, m), 7.51 (HI, br), 7.60 (1 / 2H, s) , 7.66 (1 / 2H, s), 7.80 (1 / 2H, br), 7.84 (1 / 2H, br), 8.40 (1 / 2H, s), 8.44 (1 / 2H, s) MS (ESI) -): 577.2 (MH) EXAMPLE 386 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5-. { 3- (2- (N-methoxycarbonyl-N-methylamino) acetylamino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (160 mg) NMR (CDCl 3, d): 1.46 (2H, br), 1.68 (4H, br), 1.96 (2H, br), (2H, m), 2.70-2.94 (2H,), 3.02-3.09 (2H, m) , 3.10 (3H, s), 3.16 (2H, br), 3.31-3.53 (HH, m), 3.65-3.75 (HH,), 3.80 (HH, s), 4.02-4.09 (2H, m), 4.54 ( 1 / 2H, br), 4.83 (1 / 2H, br), 7.24-7.31 (5H, m), 7.53 (1H, br), 7.63 (1 / 2H, s), 7.67 (1 / 2H, s), 8.44 (1 / 2H, s), 8.50 (1 / 2H, s) MS (ESI-): 592.1 (MH) Example 367 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [ 5- [4- (3-pyridyl-2-propyloxy) phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (270 mg) NMR (DMSO-d6, d): 1.36-1.65 (6H, m), 1.70-2.06 (4H, (HH, m), 2.91-3.28 (5H, m), 3.41-3.52 (HH, m), 3.75-3.91 (HH, m) , 4.45, 4.75 (HH, s), 3.07 (HH, d, J = 16Hz), 7.21-7.26 (HH, m), 7.30 (2H, d, J = 8.0Hz), 7.45-7.51 (2H, m) , 7.72 (2H, d, J = 8.0Hz), 7.94 (IH, d, J = 16Hz), 8.28-8.32 (IH, m), 8.60-8.62 (IH, m), 8.99 (IH, s) MS ( ESI-): 595 (MH) The following compounds were obtained in a similar manner to Example 211. Example 388 1 (1S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- (2-methoxyethoxy) acetylamino) phenyl] -2-thienyl dioxide ] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (175 mg) NMR (CDC13, d): 1.35-1.74 (8H, m), 1.89-1.99 (2H, m), 2.06- 2.25 (2H, rti), 2.68-2.89 (2H, m), 3.02-3.17 (2H, m), 3.25-3.46 (HH, m), 3.52 (3H, s), 3.58-3.67 (2H, m), 3.74-3.61 (2H, m), 4.13 (2H, s), 4.52 (1 / 2H, br), 4.79 (1 / 2H, br), 7.22-7.38 (4H, m), 7.55-7.62 (H, m) ), 7.83 (ÍH, br s), 8.04 (1 / 2H, s), 9.19 (1 / 2H, s), 8.97 (ÍH, s) MS (ESI-): 579.9 (MH) Example 389 1, 1- (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- (N-9-fluorenylmethoxycarbonyl-N-methylamino) acetylamino) phenyl) -2-thienyl] -3, 4 dioxide , 5,6-tetrahydro-2H-thiopyran-2-acetamide (1.77 g) NMR (CDC13, d): 1.42 (2H, br), 1.64 (4H, br), 1.95 (2H, br), 2.08-2.23 ( 2H, m), 2.70-2.90 (2H, m), 3.00-3.07 (5H, m), 3.10-3.16 (2H, m), 3.27-3.48 (H, m) 3.60-3.70 (H, m), 4.00 -4.0 9 (ÍH, m), 4.28 (ÍH, br), 4.52 (2H, s), 4.56 (1 / 2H, br), 4.80 (1 / 2H, br), 7.21- 7.48 (9H, m), 7.58- 7.65 (3H, m), 7.75 (2H, br), 8.20 (1 / 2H, s), 8.32 (1 / 2H, s) MS (ESI-): 791.9 (M-H + Cl) Example 390 1, 1 - (2S) -N- (2-tetrahydropyranyloxy) -2- [5-. { 3- (((2S) -2,6-bis (tert-butoxycarbonyl amino) hexanoyl) amino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (290 mg) NMR (CDC13, d): 1.45 (18H, s), 1.48-1.70 (14H, m), 1.95 (2H, br), 2.09-2.20 (2H, m), 2.68- 2.92 (2H, m), 3.00-3.15 (4H, m) 3.25-3.49 (ÍH, m), 3.63-3.74 (ÍH, m) , 4.16-4.28 (ÍH, m), 4.52 (1 / 2H, br), 4.65 (1 / 2H, br), 7.22- 7.24 (2H, m), 7.27-7.30 (2H,), 7.51 (ÍH, br ), 7.62-7.82 (HH, m) MS (ESI-): 791.3 (MH) Example 391 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2-5-. { 3- (2- te r-bu toxica rboni lamino-3- (3-pyridyl) propionylamino) phenyl} -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (1.54 g) NMR (DMSO-ds, d): 1.22-1.27 (2H, m), 1.43 (9H, s) ), 1.63-1.68 (4H, m), 1.98 (2H, br), 2.07-2.25 (2H, m), 2.74-2.98 (2H, m), 3.04-3.20 (6H, m), 3.41- 3.48 (H) , m), 3.66-3.76 (ÍH, m), 4.45 (1 / 2H, br), 4.54-4.63 (ÍH, br), 4.86 (1 / 2H, br), 5.31- 5.45 (ÍH, m), 6.82 -7.00 (2H, m), 7.04-7.20 (3H, m), 7.22-7.27 (2H, m), 7.52-7.65 (2H, m), 8.43- 8.59 (3H, m) MS (ESI-): 713.1 (M + H) Example 392 (2S) -N- (2-tetrahydropyranyloxy) -2- [5-. { 3- (3-carboxypropionylamino) phenyl} -2- thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (50 mg) in a manner similar to that of Example 3. NMR (DMSO-ds, d): 1.36-2.06 (10H , m), 2.34-2.63 (5H, m), 2.88-3.52 (6H, m), 3.65-3.90 (HI, m), 4.43 (1 / 2H, br), 4.75 (1 / 2H, br), 7.17 - 7.32 (ÍH, m), 7.28-7.48 (H, m), 8.00 (ÍH, s), 10.08 (ÍH, s), 10.59 (ÍH, s), 11.22 (ÍH, s), 12.13 (ÍH, br s) MS (ESI-): 563.4 (MH) Example 393 (2S) -N- (2-tetrahydropyranyloxy) -2- [5-. { 3- (3-methylart? Inocarbonyl) propionylamino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (50 mg) in a manner similar to that of E n emp lo 32. NMR (CDCl-dg, d): 1.48 (2H, br), 1.62 (4H, br), 1.96 (2H, br), 2.06-2.26 (2H,), 2.62-2.66 (2H, m), 2.75 (3H, br s), 2.88 (2H, br) 3.05-3.22 (5H, m), 3.36-3.49 (ÍH, m), 3.73-3.99 (ÍH, m), 4.15- 4.25 (ÍH, m), 4.70 (1 / 2H, s), 4.95 (1 / 2H, s), 6.97-7.12 (4H, m), 7.32-7.43 (2H, m), 9.12 (1 / 2H, br), 9.24 ( 1 / 2H, br) MS (ESI-): 576.3 (MH) Example 394 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3-tert-butoxycarbonylamino-) 1,1-dioxide was obtained. methyl)) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (200 mg) in a manner similar to that of Example 89. NMR (CDCl-d3, d): 1.47 (9H, s), 1.52-1.68 (6H, m), 1.81-1.95 (2H, m), 2.06-2.23 (2H, m), 2.63-2.89 (2H, m), 3.05 (2H, br s) , 3.08- 3.13 (2H,), 3.27-3.50 (ÍH, m), 3.61-3.70 (ÍH, m), 4.24-4.39 (2H, m), 4.52 (1 / 2H, br), 4.80 (1 / 2H , br), 6.71-6.82 (HH, m), 7.14-7.70 (5H, m), 8.07 (1 / 2H, s), 8.24 (1 / 2H, s) MS (ESI-): 577.3 (MH) Example 395 (2S) -N- 1,1-dioxide was obtained (2-tetrahydropyranyloxy) -2- [5-. { 3- (2- (methylamino) acetylamino) phenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (915 mg) in a manner similar to that of Example 239. NMR ( DMSO-ds d): 1.42-1.59 (6H, m), 1.73-2.05 (4H, m), (3H, s), 2.37-2.46 (ÍH, m), 2.89- 3.20 (4H, m), 3.25 ( 2H; s), 3.42-3.48 (2H, m), 3.75-3.78 (ÍH, m), 4.44 (1 / 2H, br), 4.75 (1 / 2H, br), 7.20-7.24 (ÍH, m), 7.34-7.36 (2H,), 7.38-7.42 (HH,), 7.55-7.57 (HH, m), 8.02 (HH, s) MS (ESI +): 536.3 (M + H) The following compounds were obtained in one way similar to that of Example 54. Example 396 (2S) -N-Hydroxy-2- [5- (6-methyl-3-pyridyl) -2-thienyl] -3,4,5 1,1-dioxide hydrochloride, 6-tetra there dro-2H-thiopyran-2-acetamide (89 mg). NMR (DMSO-d6, d): 1.71-2.10 (4H, m), 2.35-2.54 (HH, m) 2.68 (3H, s), 2.96-3.08 (2H, m), 3.14-3.60 (3H, m) 7.32 (ÍH, d, J = 3.5Hz), 7.74-7.81 (2H, m), 8.49 (ÍH, dd, J = 1.5, 8Hz), 9.01 (ÍH, d, J = 1. 5Hz), 10.66 (ÍH) , s) MS (ESI-): 379 (MH) Example 397 (2S) -N-hydroxy-2- (5- (6-methoxy-3-pyridyl) -2-thienyl] -3-dioxide] -3 , 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (50 mg) NMR (DMSO-ds, d): 1.71-2.09 (4H, m), 2.33-2.52 (H, m) 2.95-3.08 (2H, m), 3.10-3.29 (2H, m), 3.42-3.58 (HH, m), 3.89 (3H, s), 6.89 (HH, d, J = 8Hz), 7.21 (HH, d, J = 3.5Hz), 7.43 (IH, d, J = 3.5Hz), 7.97 (IH dd, J = 1.5, 8Hz), 8.47 (IH, d, J = 1.5Hz) MS (ESI-): 395 (MH) Example 398 (2S) -N-hydroxy-2- [5- [4- (5-methyl-1,2, -oxadiazol-3-yl) phenyl) -2-thienyl] -3-dioxide,, 5,6-tetrahydro-2H-t? Opyran-2-acetamide (67 mg) NMR (DMSO-d6, d): 1.71-2.09 (4H, m), 2.20-2.52 (H, m), 2.68 (3H, s), 2.94-3.06 (2H, m), 3.H-3.33 (2H, m), 3.36-3.56 (ÍH,), 7.26 (ÍH, d, J = 3. 5Hz), 7.63 (HH, d, J = 3.5Hz), 7.84 (2H, d, J = 8Hz), 8.03 (2H, d, J = 8Hz), 8.84 (HH, s) MS (ESI-): 446 (MH) Example 399 (2S) -N-hydroxy-2- [5- (3- (2- (acetylamino) acetylamino) -phenyl-1,1-dioxide} -2-thienyl) -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (75 mg) NMR (DMSO-d6, d): 1.69-2.08 (4H, ÍH), 1.89 (3HR, s ), 2.34-2.48 (HH, m), 2.94-3.30 (4H, m), 3.38-3.55, (HH, m), 3.88 (2H, d, J = 8.0Hz), 7.21 (HH, d, J = 4.0Hz), 7.32-7.40 (2H, m), 7.42 (HH, d, J = 4.0Hz), 7.44-7.51 (HH, m), 7.98 (HH, s), 8.22 (HH, t, J = 8.0 Hz), 8.83 (HH, s), 10.08 (HH, s), 10.60 (HH, s) MS (ESI-): 478.3 (MH) Example 400 1, 1-dioxide (2S) -N-hydroxy-2 - (5- (3-methoxycarbonyl-propionylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (60 mg). NMR (DMSO-d6, d): 1.72-2.09 (4H, m), 2.33-2.48 (HH, m), 2.63 (3H, s), 2.77-3.40 (6H, m), 3.42-3.55 (HH, m ), 7.21 (HH, d, J = 4.0Hz), 7.28-7.48 (4H, m), 7.98 (HH, s), 8.84 (HH, s), 10.12 (1H, s), 10.60 (HH, s) MS (ESI-): 493.4 (MH) EXAMPLE 401 (2S) -N-Hydroxy-2- (5-. {3- (3- (methylaminocarbonyl) -propionylamino) phenyl] -2-dioxide) -2 -thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (30 mg) NMR (DMSO-ds, d): 1.73-2.05 (4H, m), 2.40 (2H, t, J = 6.0Hz), 2.45-2.49 (ÍH, m), 2.53-2.58 (3H, m), 2.95-3.26 (4H, m), 3.40-3.54 (3H, m), 7.20 (HH, d, J = 4.0Hz), 7.32 (2H, d, J = 4.5Hz), 7.39 (HH, d, J = 4.0Hz), 7.43-7.47 (2H, m), 7.82 (ÍH, br), 8.00 (ÍH, s), 10.08 (ÍH, s), 10.60 (ÍH, s) MS (ESI-): 492.1 (MH) EXAMPLE 402 (2S) -N-Hydroxy-2- (5-. {3- (2- (2-methoxyethoxy) -acetylamino) phenyl} -2-thienyl 1,1-dioxide] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (120 mg) NMR (DMSO-d6, d): 1.70-2.07 (4H, m), 2.36-2.46 (H, m,), 2.94-3.28 (4H, m), 3.31 (3H, s), 3.48-3.51 (1H, m), 3.52-3.58 (2H, m), 3.66-3.72 (2H, m), 4.10 (2H, s), 7.22 (ÍH, d, J = 4.0Hz), 7.33-7.40 (ÍH,), 7.40 (ÍH, d, J = 4.0Hz), 7.52-7.62 (ÍH ,.), 8.00 (ÍH, s), 8.84 ( HH, s), 9.76 (HH, s), 10.60 (HH, s) MS (ESI-): 495.3 (MH) Example 403 (2S) -N-hydroxy-2- [5- (1,1- ( 3-aminomet-il-enyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (132 mg) from 1,1-dioxide (2S) -N- (2 -tetrahydropyranyloxy) -2- [5- (3- (tert-butoxycarbonyl aminom ethyl) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2-thiopyran-2-acetamide NMR (DMS06, -d): 1.73-2.08 (4H, m), 2.35-2.45 (ÍH, m). 2.95-3.26 (4H, m), 3.43-3.55 (HH,), 4.08 (2H, br), 7.24 (HH, d, J = 4.0Hz), 7.37-7.39 (HH, m), 7.45-7.50 (2H , m), 7.68 (HH, d, J = 7.5Hz), 7.75 (HH, s), 8.15 (2H, br), 8.83 (HH, s), 10.60 (HH, s) MS (ESI-): 435.2 (M-H + CH3CN) Example 404 (2S) -N-hydroxy-2- [5-. { 3- (2- (N-methoxycarbonyl-1-N-methylamino) acetylamino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (110 mg) NMR (DMSO-dg, d): 1.75-2.06 (4H, m), 2.37-2.46 (H) , m), 2.90 (3 / 2H, s), 2.94 (3 / 2H, s), 2.95-3.26 (4H, m), 3.40-3.50 (ÍH, m), 3.56 (3 / 2H, s), 3.63 (3 / 2H, s), 4.05 (2H, s), 7.20 (HH, d, J = 4.0Hz), 7.32-7.39 (3H, m), 7.42 (HH, d, J-4.0Hz), 8.02 ( ÍH, s), 8.84 (HH, s) MS (ESI-): 508.4 (MH) Example 405 (2S) -N-hydroxy-2- [5-. { 3- (((2S) -2,6-diaminohexanoyl) -amino) phenyl} -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide 1,1-dioxide (200 mg) from (2S) -N- (2-tetrahydropyranyloxy) -2- ( 5- {3- (((2S) -2,6-bis (tert-but oxycarbonyl) hexanoyl) amino) phenyl} -2-thienyl] -3,4,5,6-tetrahydro- 2H-thiopra-2-acetamide, NMR (DMSO-d6, d): 1.33-1.44 (2H, m), 1.50-1.60 (2H, m), 1.73-1.93 (4H, m), 1.95-2.07 ( ÍH, m), 2.35-2.45 (ÍH, m), 2.73-2.80 (2H,), 2.95-3.28 (4H, m), 3.50-3.55 (ÍH, m), 3.94 (ÍH, br), 7.22 (ÍH) , d, J = 4.0Hz), 7.42-7.45 (3H, m), 7.53 (IH, d, J = 7.0Hz), 7.94 (IH, s), 8.38 (IH, s) MS (ESI-): 509.3 (M + H) Example 406 (2S) -N-hydroxy-2- [5- (3- ((2S) -2-amino-3- (3-pyridyl) -propionylamino) phenyl 1,1-dioxide hydrochloride .} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (500 mg) from 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5-. {3- ((25) -2-tert-butoxycarbonyl amino-3- (3-pyridyl) propionylamino) phenyl} -2-thienyl-3,4,5,6-tetrahydro -2H-thiopyran-2-acet NMR amide (DMSO-d5, d): 1.74-2.06 (4H, m), 2.35-2.46 (HH, m), 2.97-3.34 (4H, m), 3.46-3.55 (3H, m), 4.24 (HH, br), 7.23 (ÍH, d, J-4.0Hz), 7.41-7.44 (3H, m), 7.56 (ÍH, s, J = 7.0Hz), 7.88 (ÍH, dd, J = 7.0Hz), 7.95 ( ÍH, s), 8.38 (HH, d, J = 7.0Hz), 8.48 (2H, br), 8.77 (1H, br), 8.87 (HH, brs) MS (ESI +): 529.1 (M + H) Example 407 1 (2S) -N-hydroxy-2- [5 (4- (3-pyridyl-2-propenyloxy) -phenyl) -2-t-enyl] -3,4,5,6-dioxide -tetrahydro-2H-thiopyran-2-acetamido (180 mg) NMR (DMSO-ds, d): 1.70-2.06 (4H, m), 2.36-2.47 (H, m), 2.96-3.56 (H, m) ), 7.16 (HH, d, J = 16Hz), 7.23 (HH, d, J = 4.0Hz), 7.30 (2H, d, J = 8.5Hz), 7.49 (HH, d, J = 16Hz), 7.70- 7.76 (3H, m), 7.97 (IH, d, J = 8.5Hz), 8.53-8.57 (IH, m), 8.75 (IH, d, J = 5Hz), 9.12 (IH, s), 10.6 (IH, s) MS (ESI-): 511 (MH) Example 408 (2S) -2-tert-butoxycarbonylamino-3-hydroxypropionic acid (66 mg), 1-hydroxybenzotriazole (44 mg) and l-ethyl-3 hydrochloride were added. -3-dimethylaminopropyl) c arbodiimide (62 mg) in N, N-dimethylformamide (1.3 ml) to a solution of (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3-aminophenyl) -2-thienyl 1,1-dioxide ] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (100 mg) in N, N-dimethylformamide (0.5 ml) at room temperature. After stirring at the same temperature overnight, ethyl acetate was added to the reaction mixture and the solution was washed, successively, with water, an aqueous solution of 5% citric acid, an aqueous solution of bicarbonate of saturated sodium and brine, dried over anhydrous magnesium sulfate and evaporated. After dissolving the residue in methanol (1 ml), 4N hydrochloric acid in ethyl acetate was added to the solution. The mixture was stirred at room temperature for 1 hour. After evaporating the solution under a nitrogen atmosphere, the residue was purified by reverse phase HPLC (0.1% trifluoroacetic acid in acetonitrile, gradient 1-60%) to give (2S) -N-hydroxy-1,1-dioxide. 2- (5- { 3- (((2S) -2-amino-3-hydroxypropionyl) amino) phenyl} -2-thienyl] -3,, 5,6-tetrahydro-2H-thiopyran-2 -acetamide (30 mg) as a white powder.

NMR (DMSO-d6, d): 1.76-2.10 (4H, m), 2.38-2.40 (HH, m), 3.00 (2H, d, J = 10Hz), 3.13-3.52 (4H, m), 3.82-3.93 (ÍH,), 3.98-4.06 (ÍH, m), 7.23 (ÍH, d, J = 4.0Hz), 7.40-7.45 (3H, m), 7.50-7.54 (ÍH, m), 7.98 (ÍH, s) , (2H, br), 10.73 (HH, s) MS (ESI +): 468.3 (M + H) The following compound was obtained in a manner similar to that of Example 408. Example 409 (2S) - 1,1-dioxide - N-hydroxy-2- [5- (3- (2-dimethyl aminocarbonyl) amino) -acetylamino) phenyl} -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (30 mg) from 1,1-dioxide (2S) -N- (2-tetrahydropyranyl) -2- [5- . { 3- ((2-aminoacetyl) amino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (150 mg) and dimethylaminocarbonyl chloride. NMR (DMSOd6, d): 1.74-2.04 (4H,), 2.35-2.44 (HH, m), 2.85 (6H, s), 2.95-3.25 (4H, m), 3.46-3.53 (HH, m), 3.78 (2H, d, J = 4.0Hz), 6.65 (ÍH, t, J = 4.0Hz), 7.2 0 (ÍH, d, J = 4.0Hz), 7.34-7.40 (2H, m), 7.40-7.48 (2H , m), 8.01 (OH, s), 8.08 (OH, br), 9.98 (OH, s) 10.60 (OH, s) MS (ESI +): 509.2 (M + H) Example 410 1,1-dioxide was obtained of (2S) -N-hydroxy-2- [5-3- (2- (N- (dimethylaminocarbonyl) -N-methylamino) acetylamino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (30 mg) in a manner similar to that of Example 409. NMR (DMSO-ds, d): 1.73-2.05 (4H ,), 2.37-2.48 (HH, m), 2.74 (6H, s), 2.87 (3H, s), 2.95- 3.25 (4H, m), 3.44-3.52 (HH, m), 3.91 (2H, s) , 7.20 (HH, d, J = 4.0Hz), 7.34-7.45 (3H, m), 7.42 (HH, d, J = 4.0Hz), 8.02 (HH, s), 10.06 (HH, s), 10.60 ( ÍH, s) MS (ESI-): 521.2 (MH) Example 411 (2S) -N- [2-tetrahydropyranyloxy) -2- [5- (4- (5-methyl-1,2,4-oxadiazole -3-yl) phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide 1,1-dioxide (113 mg) in a manner similar to that of Example 201. NMR ( CDC13, d): 1.38-1.74 (6H, m), 1.90-2.01 (2H, m), 2.06-2.25 (2H, m), 2.67 (3H, s), 2.70-2.89 (2H, m), 3.03- 3.03 (2H, m), 3.10- 3.18 (2H, m), 3.28-3.50 (HH, m), 3.59-3.72 (HH, m), 4.53 (0.5H, s), 4.81 (0.5H, s), 7.28-7.32 (ÍH, m), 7.35-7.39 (ÍH, m), 7.71 (2H, d, J = 8Hz), 7.99 (0.5H, s), 8.08 (2H, d, 3-8Hz), 8.13 ( 0.5H, s) MS (ESI-): 530 (MH) E Example 412 Tert-butyl 2- (5-bromo-2-thienyl) -2,3,4,5,5-tetrahydrothiophene-2-acetate (2.77 g) was obtained in almost the same manner as that of Example 93. NMR (CDC13, d): 1.34 (9H, s), 1.90-2.05 (HH, m), (2H, m), 2.26-2.36 (HH, m), 2.83 (HH, d, J = 15Hz), 2.98-3.09 (2H) , m), 3.12 (HH, d, J = 15Hz) 6.70 (HH, d, J = 4Hz), 6.87 (2H, d, J = 4Hz) Example 413 Tert-butyl 2- [5- (4- fluorophenyl) -2-thienyl] -2, 3, 4, 5-tetrahydrothiophene-2-acetate (479 mg) in almost the same manner as that of Example 100. NMR (CDCl 3, d): 1.34 (9H, s), 2.02 -2.29 (3H, m), 2.36-2.46 (HH, m), 3.00 (HH, d, J = 16Hz), 3.01-3.14 (2H, m), 3.17 (HH, d, J = 16Hz), 6.92 ( ÍH, d, J = 4Hz), 7.00-7.08 (3H, m), 7.52 (2H, dd, J = 4, 9Hz) Example 414 2- [5- (Fluorophenyl) -2-thienyl) -2 was obtained , 3,4, 5-tetrahydrothiophene-2-acetic acid (298 mg) in a manner similar to that of Example 95. NMR (CDCl 3, d): 2.02-2.31 (3H, m), 2.39-2.50 (1H, m), (3H, m), 3.30 (HH, d, J = 16Hz), 6.93 (HH, d, J = 4Hz), 6.99-7.06 (3H, m), 7.5 0 (2H, dd, J = 5, 9Hz) MS (ESI-): 321 (MH) Example 415 1, 1-2- [5- (4-fluorophenyl) -2-thienyl] -2 acid dioxide was obtained , 3, 4, 5-tetrahydrothiophene-2-acetic acid (272 mg) in a manner similar to that of Preparation 1-4) NMR (COd3, d): 2.18-2.43 (2H, m), 2.70-2.82 (OH, m), 2.89-3.01 (HH, m), 3.09 (HH, d, J = 16Hz), 3.14-3.25 (2H, m), 3.36 (HH, 6, J = 16Hz), 7.07 (2H, t, J = 9Hz), 7.13-7.19 (2H, m), 7.54 (2H, dd, J = 5, 9Hz) The following compounds were obtained in a manner similar to that of Example 130. Example 416 (2S) 1,1-dioxide -N- (2-tetrahydropyranyloxy) -2- [5-. { 3- (2- (benzyloxycarbonylamino) acetylamino) phenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (230 mg) NMR (CDC13, d); 1.43 (4H, br), 1.63-1.65 (2H, m), 1.94 (2H, br), 2.09-2.23 (2H, m), 2.82 (2H, br), 3.06-3.17 (4H, m), 3.27- 3.50 (ÍH, m), 3.64-3.76 (ÍH, m), 4.03-4.05 (2H, m), 4.52 (1 / 2H, br), 4.83 (1 / 2H, br), 5.18 (2H, s), 7.10-7.22 (4H, m), 7.30-7.38 (6H, m), 7.45-7.55 (2H, m), 8.23 (ÍH, br), 8.77 (1 / 2H, br), 8.85 (1 / 2H, br) MS (ESI-): 654.2 (MH) Example 417 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5-. { 3- (2- (4-methoxybenzene sulfonylamino) acetylamino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (220 mg) NMR (CDC13, á): 1.43 (4H, br), 1.62-1.72 (2H, m), 1.95 (2H br), 2.06-2.25 (2H, m), 2.75- 2.90 (2H, m), 3.00-3.18 (4H, m), 3.28-3.50 (ÍH,), 3.64-3.70 (ÍH, m), 3.75 (2H, d, J = 6.0Hz), 3.82 (3H, s), 4.54 (1 / 2H, br), 4.85 (1 / 2H, br), 5.72-5.86 (ÍH,), 6.98 (2H, 6 , J = 8.0 Uz), 7.14-7.23 (4H,), 7.85 (2H, d, J = 8.0Hz), 8.40 (1H, br), 8.78 (1 / 2H, s), 8.94 (1 / 2H, s ) MS (ESI-): 690.1 (MH) Example 418 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- [3- [2- (1, 5, 5, 1,1-dioxide) was obtained -trimethylhydantoin-3-yl) acetylamino] phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (212 mg) in a manner similar to that of Example 211. NMR (CDCI3, d): 1.38-1.75 (12H, m), 1.87-2.05 (2H,), 2.07-2.28 (2H;), 2.77-2.96 (5H, m), 3.00-3.25 (4H, rti), 3.27-3.54 (HH,), 3.68-3.81 (HH,), 4.40 (2H, s), 4.53 (0.5H, s), 4.85 (0.5H, s), 6.93-7.06 (HH, m) , 7.09- 7.34 (4H, m), 7.54-7.66 (ÍH, rti), 8.25-8.35 (ÍH, m), 9.05 (0.5H, s), 9.20 (0.5H, s) MS (ESI-): 645 (MH) EXAMPLE 419 (2S) -N-2-Tetrahydro-pyranyloxy) -2- [5- [4- (phenoxycarbonyloxymethyl) phenyl] -2-thienyl] -3,4,5 1,1-dioxide, 6-1etrahydro-2H-thiopyran-2-acetamide (120 mg) in a manner similar to that of Example 244. NMR (CDC13, d): 1.35-1.76 (6H, m), 1.87-2.00 (2H, m), 2.04 - 2.25 (2H, m), 2.65-2.91 (2H, m), 3.00-3.18 (4H,), 3.25-3.51 (HH, m), 3.59-3.72 (HH, m), 4.53 (0.5H, s) , 4.81 (0.5H, s), 5.27 (2H, s), 7.17 (2H, d, J = 8Hz), 7.23-7.32 (ÍH,), 7.35-7.49 (6H, m), 7.62 (2H, 6, J = 8Hz), 8.01 (0.5H, s), 8.15 (0.5H, s) MS (ESI-): 598 (MH) Example 420 There was obtained 1,1-dioxide (2S) -N- (2-tetra hydropyranil oxy) -2- [5- [4- (methylaminocarbonyl loxymethyl) phenyl] -2-thienyl} 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (70 mg) in a manner similar to that of Example 245.

NMR (CDCI3, d): 1.36-1.75 (6H, m), 1.86-2.01 (2H, m), 2.05-2.24 (2H, m), 2.64-2.55 (5H, m), 3.01-3.18 (4H, m) ), 3.27-3.50 (HH, m), 3.56-3.70 (HH, m), 4.53 (0.5H, s), 4.61-4.74 (HH, m), 4.80 (0.5H, s), 5-H (2H) , s), 7.21- 7.29 (2H, m), 7.36 (2H, d, J = 8Hz), 7.56 (2H, d, J = 8Hz), 7.96 (0.5H, s), 8.11 (0.5H, s) MS (ESI-): 535 (MH) Example 421 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- [5- (methoxycarbonylamino) -3-pyridyl) 1,1-dioxide was obtained) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (170 mg) in a manner similar to that of Example 201. NMR (CDCl 3, d): 1.40-1.74 (6H, m ), 1.89-2.01 (2H, m), 2.05-2.25 (2H, m), 2.70-2.95 (2H, m), 3.01-3.17 (4H, m), 3.30-3.56 (HI, m), 3.62-3.76 (HH, m), 3.83 (3H, s), 4.53 (0.5H, s), 4.84 (0.5H, s), 6.97-7.06 (HH, m), 7.25- 7.33 (HH, m), 7.36-7.65 (HH, m), 8.10-8.19 (HH,), 8.40-8.56 (3H,) MS (ESI-): 522 (MH) Example 422 1,1-Dioxide of (2S) -N- (2- tetrahydropyranyloxy) -2- [5- (3- (methylamine indocarbonyl-methylaminocarbonylamino) phenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (45 mg) in a manner similar to that of Example 32. NMR (CDC13, d): 1.40 -1.47 (4H, m), 1.64-1.69 (2H, m), 2.15 (2H, br), 2.28 (2H, br), 2.80 (3H, br s), 2.81-2.88 (2H, m), 2.98- 3.15 (4H, m), 3.25- 3.52 (1H, m), 3.72-3.81 (HI, m), 3.85-3.94 (2H,), (1 / 2H, br), 4.85 (1 / 2H, br), 5.27-5.43 (HH, m), 7.12-7.19 (6H, m), 7.48-7.55 (2H, m), 7.67-7.72 (HH, m) MS (ESI-): 577.2 (MH) Example 423 Obtained 1 , (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (carboxymethylamino-carbonylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2R-1-dioxide thiopyran-2-acetamide (130 mg) in a manner similar to that of Example 3. NMR (CDCl 3, d): 1.43-1.50 (2H, m), 1.64-1.68 (4H, m), 1.92 (2H, br), 2.08-2.21 (2H, m), 2.40-2.48 (2H, m), 2.95-3.14 (4H, m), 3.30- 20 3.53 (HH, m), 3.75-3.81 (HH, m), 4.00 (2H, br s), 4.45 (1 / 2H, br), (1 / 2H, br), 7.15- 7.22 (5H, m), 7.53 (1 / 2H, s), ( 1 / 2H, s) MS (ESI-): 565.0 (M-H) The following compounds were obtained in a manner similar to that of Example 249.

A ^^ * & AÍ - z¿ * i: EXAMPLE 424 1 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- (allylamino) acetylamino) phenyl) -2-thienyl] -3,4,5,5-dioxide 6-tetrahydro-2H-thiopyran-2-acetamide (106 mg) NMR (CDCl 3, d): 1.45 2H, br), 1.64-1.68 (4H, m), 1.95 (2H, br), 2.06-2.24 (2H, m), 2.64-2.86 (2H, m), 3.07 (2H, br s), 3.13-3.16 (2H, m), 3.30-3.49 (ÍH, m), 3.46 (3H, d, J = 7.0Hz), 3.45 (2H, s), 3.62-3.71 (HH, m), 4.52 (1 / 2H s), 4.80 (1 / 2H, s), 5.20-5.30 (2H, m), 5.85- 5.98 (HH, m) , 7.23-7.32 (4H, m), (HH, br), 7.80 (HH, s), 9.40 (HH, s) MS (ESI +): 562.2 (M + H) Example 425 1, 1-dioxide (2S) ) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- (2-ethoxyethyl) amino) acetylamino) phenyl} -2-thienyl] -3,4,5,6-tetrahydro-2H -thiophen-2-acetamide (65 mg) NMR (CDCI3, d): 1.23 (3H, t, J = 7.5Hz), 1.46 (2H, br), 1.65-1.80 (4H, m), 1.95 (2H, br), 2.05- 2.25 (2H, m), 2.65- 2.85 (HH, m), 2.88 (2H, t, J = 6.0Hz), 3.30-3.49 (HH, m), 3.44 (2H, s), 3.51-3.58 (4H, m), 3.62-3.70 (HH, m), 4.52 (1 / 2H, br), 4.80 (1 / 2H, br), 7.27-7.35 (5H, m), 7.57-7.61 (H, m), 7.83 (H, s) 8.03 (1 / 2H , br), 8.20 (1 / 2H, br s), 9.52 (OH, s) MS (ESI +): 594.2 (M + H) Example 426 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- (benzylamino) acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (95 mg) NMR (CDC13, d): 1.43 (2H, br), 1.52-1.68 (4H, m), 1.96 (2H, br), 2.10-2.22 (2H, m, 2.66- 2.89 (2H, m), 3.06 (2H, br s) , 3.10-3.16 (2H, m), 3.29-3.50 (ÍH, m), 3.45 (2H, br s), 3.60-3.70 (ÍH, m), 3.88 (2H, s), 4.52 (1 / 2H, br ), 4.80 (1 / 2H, br), 7.27-7.38 (lOH, m), 7.52 (HH, br), 7.79 (HH, br), 8.05 (1 / 2H, br), 8.20 (1 / 2H, br ), 9.33 (H, s) MS (ESI +): 612.2 (M + H) Example 427 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- (p ent i lame) acetylamino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (83 mg) NMR (CDCI3, d): 0.87-0.94 (5H, m), 1.29-1.64 (6H, m ), 1.42-1.64 (4H, m), 1.95 (2H, br), 2.08-2.22 (2H, m), 2.62-2.88 (2H, m) 1 2.69 (2H, t, J = 7.0Hz), 3.06 ( 2H, s), 3.10-3.14 (2H, m), 3.24-3.50 (HH,), 3.39 (2H. S), 3.61-3.69 (HH, m), 4.54 (1 / 2H, br), 4.80 (1 / 2H, br), 7.25-7.33 (5H, m), 7.56 (IH, br), 7.80 (IH, s), 8.00 (1 / 2H, br), 8.16 (1 / 2H, s), (ÍH, s) MS (ESI +): 592.3 (M + H) Example 428 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- (5- (3- ((2R) -2-ter- butoxycarbonylamino-3-benzyloxypropionyl) aminophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (400 mg) NMR (CDC13, d): 1.40-1.48 (2H, br) , 1.49 (9H, s), 1.60-1.68 (4H, m), 1.94 (2H, br), 2.06- 2.24 (2H, m), 2.65-2.90 (2H, m), 3.06 (ÍH, br s), 3.11-3.16 (2H, br), 3.27-3.47 (HH, m), 3.63-3.70 (2H, m), 3.97-4.04 (HH, m), 4.44 (HH, br), 4.52 (1 / 2H) , br), 4.55 (HH, d, J = 1.0Hz), 4.65 (HH, d, J = 10Hz), 4.80 (1 / 2H, br), 5.50 (HH, br), 7.22-7.41 (HH, m), 7.72 (HH, br), 8.07 (1 / 2H, s), 8.20 (1 / 2H, s), (1H, br) MS (ESI-): 776.2 (M-H + Cl) The following compounds were obtained in a manner similar to that of Example 54. Example 429 (2S) 1,1-dioxide - N-hydroxy-2- (5- (3-cyclobutane carbonyl aminophenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (250 mg) NMR (DMSO-ds, d) ): 1.75-2.30 (HH, m), 2.37-2.46 (HH, m), 2.95-3.52 (5H, m), 7.20 (HH, d, J = 4.0Hz), 7.33-7.35 (2H, m), 7.40 (ÍH, d, J = 4.0Hz), 7-46-7.50 (ÍH, m), 8.02 (ÍH, s), 9.84 (ÍH, s), 10.60 (ÍH, s) MS (ESI-): 461 (MH) Example 430 (2S) -hydroxy-2-5- [3- [2- (1, 5, 5-trimethylhydantoin-3-yl) acetylamino] phenyl] -2-thienyl 1,1-dioxide) - 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (117 mg) NMR (DMSO-d6, d): 1.36 (6H, s), 1.70-2.09 (4H, m), 2.35-2.54 ( ÍH, m), 2.84 (3H, s), 2.94- 3.08 (2H, m), 3.10-3.29 (2H,), 3.36-3.55 (ÍH, m), 4.23 (2H, s), (ÍH, d, J = 3.5H z), 7.35-7.43 (4H, m), 7.95 (HH, s), 8.63 (HH, s), 10.41 (HH, s), 10.60 (HH, s) MS (ESI-): 561 (MH) Example 431 (2S) -N-hydroxy-2- [5- [4- (methylaminocarbonyloxymethyl) -phenyl-3-2-thienyl] -3-4-5-6-tetrahydro-2H-thiopyran 1,1-dioxide -2 acetamide 1,1-dioxide (46 mg) NMR (DMSO-d6, d): 1.67-2.09 (4H, m), 2.34-2.53 (HH, m), 2.59 (3H, d, J = 4.8Hz ), 2.94-3.08 (2H, m), 3.10-3.30 (2H, m), 3.38-3.55 (HH, m), 5.02 (2H, s), 7.21 (HH, d, J = 3.5Hz), 7.38 ( 2H, d, J = 8Hz), 7.48 (IH, d, J = 3.5Hz), 7.64 (2H, d, J = 8Hz), 8.85 (IH, br s) MS (ESI-): 451 (MH) Example 432 (2S) -N-hydroxy-2- (5- [5- (methoxycarbonyl amino) -3-pyridyl] -2-thienyl] -3,4,5,6-tetrahydro-2H- 1,1-dioxide thiopyran-2-acetamide (94 mg) NMR (DMSO-ds, d): 1.71-2.09 (4H, m), 2.35-2.56 (H, m) 2.95-3.06 (2H, m), 3.H-3.32 ( 2H, m), 3.41-3.57 (HH, m), 3.74 (3H, s), 7.29 (HH, d, J = 3.5Hz), 7.65 (HH, d, J = 3.5Hz), 8.32 (HH, s ), 8.63 (ÍH, d, J = 1.5Hz), 8.71 (ÍH, d, J = 1.5Hz) MS (ESI + ): 440 (M + H) Example 433 1, (2S) -N-hydroxy-2- [5- [3- (2, 2-dimethylpropionylamino) -phenyl] -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran -2 acetamide (100 mg) NMR (DMSO-dg, d): 1.24 (9H, s), 1.71-2.08 (4H, m), 2.35-2.53 (HH, m), 2.94-3.07 (2H, m), 3.10-3.2, (2H, m), 3.39-3.55 (HH, m), 7.20 (HH, da, J = 3.5Hz), 7.30-7.39 (2H, m), 7.41 (HH, d, J = 3.5Hz ), 7.59-7.65 (HH, m), 8.01 (HH, s), 8.84 (HH, brs), 9.30 (HH, s) MS (ESI-): 463 (MH) Example 434 1,1-dioxide (2S) -N-hydroxy-2- [5- [3- ((E) -2-butenoylamino) phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2- acetamide (104 mg) NMR (DMSO-ds, d): 1.71-2.08 (7H, m), 2.36-2.55 (HH, m), 2.94-3.08 (2H, m), 3.10-3.29 (2H, m), 3.39-3.85 (ÍH, m), 6.14 (ÍH, dd, J = 1.5, 14Hz), 6.75-6.88 (ÍH, m), 7.21 (ÍH, 6, J = 3.5Hz), 7.32-7.39 (2H m) , 7.41 (HH, d, J = 3.5Hz), 7.50-7.56 (HH, m), 8.05 (HH, s), 10.05 (HH, s), 10.60 (HH, s) MS (ESI-): 447 ( MH) Example 435 (2S) -N-hydroxy-2- (5-. {3- (2- ( benzyloxy carboni lamino) -acetylamino) phenyl} -2-thienyl) -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (150 mg) NMR (DMSO-dβ, d): 1.75-2.06 (4H, m), 2.38-2.47 (HH) , m), 2.96-3.27 (4H,), 3.40-3.55 (HH, m), 3.83 (2H, d, J = 6.5Hz), 5.06 (2H, s), 7.22 (HH, d, J = 4.0Hz ), 7.29-7.40 (8H, m), 7.45-7.50 (ÍH, m), 7.58 (ÍH, t, J = 6.5Hz), 8.00 (ÍH, s), 8.84 (ÍH, br), 10.10 (ÍH, s), 10.60 (HH) MS (ESI-): 570.1 (MH) Example 436 (2S) -N-hydroxy-2- [5- (3- (2- (4-methoxybenzenesulfonylamino) 1,1-dioxide) acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (170 mg) NMR (DMSO-ds, d): 1.73-2.05 (4H, m), 2.35 -2.46 (HH, m), 2.95-3.26 (4H, m), 3.49-3.53 (HH, m), 3.62 (2H, s), 3.77 (3H, s), 7.08 (2H, d, J = 8.0Hz ), 7.20 (HH, d, J = 4.0Hz), 7.30-7.38 (4H, m), 7.75 (12H, d, J = 8.0Hz), 7.84 (HH, s), 8.84 (HH, br), 10.02 (HH, s) MS (ESI-): 606.2 (MH) Example 437 (2S) -N-hydroxy-2- [5- (3- (methylammo-15-carbonylmethylaminocarbonylamino) phenyl) -2-thienyl 1,1-dioxide ] -3, 4, 5, 6- tetrahydro-2H-thiopyran-2-acetamide (25 mg) NMR (DMSO-d6, d): 1.72-2.08 (4H, m), 2.36-2.45 ™ (H, m), 2.61 (3H, d, J = 4.5 Hz), 2.95-3.25 (4H, m), 3.42-3.50 (ÍH, m), 3.70 (2H, d, 20 J = 6.5Hz), 6.45 (ÍH, t, J = 6.5Hz), 7.17-7.27 ( 4H, m), 7.37 (IH, d, J = 4.0Hz), 7.84 (4H, s), 7.88 (IH, br), 8.84 (IH, br), 9.01 (IH, s), 10.63 (IH, s ) MS (ESI-): 493.3 (MH) 25 Example 438 _- ^ &tt ^ (2S) -N-hydroxy-2- (5-. {3- (((2R) -2-a-ino-3-benzyloxypropyl) amino) 1,1-dioxide phenyl.} -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide 1,1-dioxidohydrochloride (125 mg) from (2S) -N- (2-tetrahydropyranyloxy) -2- (5- { 3- (((2R) -2-tert-butoxy carbonylamino-3-benzyloxypropionyl) amino) phenyl) -2-thienyl] -3,, 5,6-tetrahydro-2H-thiopyran -2-acetamide NMR (DMSO-d6, d): 1.73-2.06 (4H, m), 2.36-2.46 (HH, m), 2.95-3.26 (4H, m), 3.40-3.55 (HH, m) , 3.48 (2H, d, J = 4.5Hz), 4.26 (IH, br t, J = 4.5Hz), 4.58 (2H, d, J = 5.0Hz), 7.23 (IH, d, J = 4.0Hz), 7.27-7.35 (6H, m), 7.40-7.44 (2H, m), 7.53 (IH, d, J = 6.0Hz), 7.94 (IH, s), 8.41 (2H, br), 8.83 (IH, s) 10.62 (HH, s), 10.62 (HH, s) MS (ESI-): 558.3 (MH) Example 439 1, 1-dioxide (2S) -N-hydroxy-2- [5- (3- (2 - (allylamino) acetylamino) -phenyl) -2-t-enyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (70 mg) NMR (DMSO-d6, d): 1.75- 2.06 (4H, m), 2.36-2.45 (HH, m), 2.96-3.27 (4H, m), 3.40-3.50 (HH, m), 3.69 (2H, d, J = 6.0Hz), 3.93 (2H, s), 5.42-5.54 (2H, m ), 5.84-5.98 (HH, m), 7.22 (HH, d, J = 4.0Hz), 7.38-7.45 (3H, m), 7.48-7.52 (HH, m), 7.95 (HH, s), 8.85 ( 1H, br), (HH s), 10.77 (HH, s) MS (ESI-): 476.1 (MH) Example 440 1,1-dioxide. (2S) -N-hydroxy-2- [5- (3- (2- (2-ethoxyethylamino) -acetylamino) phenyl} -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran -2-acetamide (45 mg) NMR (DMS0-d6, d): 1.14 (3H, t, J = 7.0Hz), 1.74- 2.06 (4H, m), 2.35-2.45 (H, m), 2.93-3.26 (4H, m), 3.41-3.47 (ÍH, m), 3.57 (2H, d, 3-7.0, 7.0Hz), 3.55 (2H, t, J = 4.5Hz), 3.65 (2H, s), 7.22 ( ÍH, d, J = 4.0Hz), 7.38-7.44 (3H, m), 7.50-7.54 (ÍH, m), 7.98 (ÍH, s) 8.84 (ÍH, s), 10.33 (ÍH, br), 10.62 ( ÍH, s) MS (ESI-): 508.2 (MH) Example 441 (2S) -N-hydroxy-2- [5-. { 3- (2-pentylamino) acetylamino) phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (55 mg) NMR (DMSO-dg, d): 0.90 (3H , t, J = 4.5Hz), 1.24- 134 (4H, m), 1.63 (2H, br), 1.73-2.05 (4H, m), 2.37-2.46 (ÍH, m), 2.92-3.28 (6H, m ), 3.43-3.53 (HH, m), 3-92 (2H, s), 7.22 (HH, d, J = 4.0Hz), 7.38-7.44 (3H, m), 7.50-7.54 (HH, m), 7.96 (HH, s), 8-84 (2H, br s), 10.64 (HH, s), 10.75 (HH, s) (ESI +): 508.1 (M + H) Example 442 1,1-dioxide (2S) ) -N-hydroxy-2- (5- (3-isobutyryl aminophenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopi ran-2-acetamide (250 mg) NMR (DMS0-d3) , d): 1.11 (6H, d, J = 7.0Hz), 1.70-2.08 (4H,), 2.35-2.45 (HH, m), 2.55-2.64 (HH, m), 2.95-3.54 (5H, m) , 7.20 (HH, d, J = 4.0Hz), 7.34-7.35 (2H, m), 7.40 (HH, d, J = 4.0Hz), 7.46-7.51 (HH, m), 6.01 (HH, s), 8.84 (OH, s), 9.94 (OH, s), 10.60 (OH, s) MS (ESI-): 449 (MH) Example 443 (2S) -N-hydroxy-2- [1,1-dioxide] - (3- (2-benzylamino) acetylamino) -phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (55 mg) NMR (DMS0-66, d): 1.74-2.06 (4H, m), 2.35-2.45 (H) , m), 2.95-3.28 (4H, m), 3.40-3.50 (3H, m), 3.89 (HH, s), 4.24 (HH, s), 7.22 (HH, d, J = 4.0Hz), 7.36- 7.55 (9H, m), 7.92 (OH, s), 8.84 (OH, s), 10.62 (OH, s) MS (ESI-): 528.1 (MH) The following compounds were obtained in a manner similar to that of Example 408 .

Example 444 1-1 (2S) -N-hydroxy-2- [5-] dioxide. { 3- (((2S) -2-amino-3-benzyloxypropionyl) amino) phenyl) -2-thienyl} -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (40 mg) from L-Boc-Ser (bzl) -OH NMR (DMS0-d6, d): 1.73-2.06 (4H, m), 2.36-2.46 (HH, m), (4H, m), 3.40-3.55 (HH, m), 3.48 (2H, d, J = 4.5Hz), 4.26 (HH, br t, J = 4.5Hz ), 4.58 (2H, d, J = 5.0Hz), 7.23 (HH, d, J = 4.0Hz), 7.27-7.35 (6H, m), 7.40-7.44 (2H, m), 7.53 (HH, d, J = 6.0Hz), 7.94 (HH, s), 8.41 (2H, br), 8.83 (HH, s), 10.62 (HH, s), 10.82 (HH, s) MS (ESI +): 558.3 (M + H Example 445 (2S) -N-hydroxy-2- [5-3 - ((2S) -2-pyrrolidinylcarbonylamino) phenyl 1,1-dioxide} -2-thienyl) -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (40 mg) from L-Boc-Pro-OH NMR (DMSO-d6, d): 1.84-2.05 ( 7H, m), 2.35-2.45 (2H, m), (4H,), 3.44-3.53 (3H, m), 4.35 (ÍH, br), 7.22 (ÍH, d, J = 4.0Hz), 7.39-7.50 (4H, m), 7.96 (ÍH, s), 8.72 (ÍH, br), 8.83 (ÍH, s), 9.27 (1H, br) MS (ESI +): 468.3 (M + H) Example 446 1, 1-dioxide (2S) -N-hydroxy-2- [5- (3- ((2S) -2-amino- 3-cyclohexylpropionyl) amino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (50 mg) from L-Boc-CHA-OH NMR (DMSO-ds, d): 0.87-0.98 ( 2H, m), 1.10-1.25 (4H, m), 1.40 (HH, br), 1.60-1.77 (6H, m), 1.85-2.06 (4H, m), 2.35-2.47 (HH, m), 2.95- 3.27 (4H, m), 3.44-3.53 (HH, m), 3.96 (HH, br), 7.22 (HH, d, J = 4.0Hz), 7.40-7.48 (3H,), 7.60 (HH, d, J = 7.0Hz), 7.90 (HH, s), 8.23 (2H, br), 8.84 (HH, s), 10.55 (HH, s), 10.60 (HH, s) MS (ESI +): 534.8 (M + H) Example 447 (2S) -N-hydroxy-2- [5- (3- ((2-amino-2-methylpropionyl) amino) phenyl) -2-thienyl] -3,5,5-dioxide 6-tetrahydro-2H-thiopyran-2-acetamide (20 mg) from L-BOC-AiB-OH NMR (DMSO-d6, d): 1.62 (6H, s), 1.74-2.06 (4H,), 2.35-2.44 (HH, m), 2.95-3.27 (4H, m), 3.37-3.53 (1H, m) , 7.22 (HH, d, J = 4.0Hz), 7.38-7.48 (3H, m), 7.60 (HH, d, J = 7.5Hz), 7.92 (HH, s), 8.24 (2H, br), 8.83 ( ÍH, s) MS (ESI +): 466.3 (M + H) Example 448 (2S) -N-hydroxy-2- [5- (3- (((2R) -2-methoxypropionyl) amino] 1,1-dioxide ) phenyl.} -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (30 mg) NMR (DMSO-d6, d): 1.32 (3H, d, J = 6.0 Hz), 1.73- 2.06 (4H, m), 2.36-2.43 (HH, m), 2.95-3.26 (4H, m), 3.34 (3H, s), 3.45-3.54 (HH, m), 3.87 (HH, q, J = 6.0Hz), 7.20 (HH, d, J = 4.0Hz), 7.32-7.35 (2H, m), 7.40 (HH, d, J = 4.0Hz), 7.62 (HH, d, J = 6.5 Hz), 8.60 (ÍH, s), (ÍH, s), 10.60 (1, s) MS (ESI-): 465.2 (MH) Example 449 (2S) -N-hydroxy-2-1,1-dioxide [5- (3- (((2S), -2-amino-4-carboxybutyryl) amino) phenyl] -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (33 mg) from L-Boc-Glu (tBu) -OH NMR (DMSO-d6, d): 1.74-2.25 (6H, m), 2.37 -2.46 (HH, m), 2.95-3.26 (4H, m), 3.45-3.62 (HH, m), 3.95-4.04 (3H, m), 7.23 (HH, d, J = 4.0Hz), 7.40-7.45 (3H, m), 7.52 (HH, d, J = 7.0Hz), 7.90 (HH, s), 8.28 (2H, br), (HH, br) MS (ESI +): 510.7 (M + H) Example 450 (2S) -N-hydroxy-2- [5- (3- (2- (benzoylamino) acetylamino) -phenyl-1,1-dioxide} -2-thienyl) -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (42 mg) NMR (DMSO-d6, d): 1.72-2.04 (4H, m), 2.36-2.47 (H) , m), 2.95-3-25 (4H, m), 3.43-3.53 (HH, m), 4.09 (2H, d, J = 6.0Hz), 7.20 (HH, d, J = 4.0Hz), 7.36- 7.39 (2H, m), 7.42 (HH, d, J = 4.0Hz), 7.47-7.57 (4H, m), 7.92 (2H, d, J = 7.5Hz), 8.30 (HH, s), 8.88 (HH) , t, J = 6.0Hz), 10.20 (HH, s), 10.60 (HH, s) MS (ESI-): 541.3 (MH) Example 451 (2S) -N-hydroxy-2-1,1-dioxide - [5- . { 3- (2- (ethylamino) acetylamino) -phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (60 mg) from 2- (N-ethyl) N-tert-butoxycarbonylamino) acetic NMR (DMSO-d6, d): 1.22 (3H, t, J = 7.0Hz), 1.74- 2.06 (4H, m), 2.35-2.45 (HH.m.), 2.95-3.27 ( 6H, m), 3.51-3.57 (HH, m), 3.96 (2H, t, J = 5.0Hz), 7.22 (HH, d, J = 4.0Hz), 7.42-7.46 (3H, m), 7.48-7.51 (HH, m), 7.93 (HH, s), 8.87 (2H, br), 10.60 (HH, s), 10.54 (HH, s) MS (ESI +): 466.2 (M + H) Example 452 1.1- (2S) -N-hydroxy-2- [5-. { 3- (((25) -2- (aminobutyryl) amino) -phenyl} -2-thienyl] -3,4,5,6-tetrahydro- ? M 2 H -thiopyran-2-acetamide (105 mg) from L-Boc-Abu-OH NMR (DMSO-ds, d): 0.98 (3H, t, J = 6.5Hz), 1.74- 2.06 (4H, m ), 1.89 (2H, qt, J = 6.5, 6.5Hz), 2.36-2.45 (1H, m), 2.96-3.27 (4H, m), 3.44- 3.54 (HH, m), 3.90 (HH, br), 7.22 (ÍH, d, J = 4.0Hz), 7.39-7.46 (3H, m), 7.52-7.56 (ÍH, m), 7.91 (ÍH, s), 8.32 (2H, br), (ÍH, s), 10.56 (HH, s), 10.60 (HH, s) MS (ESI +): 467.2 (M + H) Example 453 1, 1-di (2S) -N-hydroxy-2- [5-. { 3- (2- (piperizin carbonyloxy) acetylammo) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (47 mg) NMR (DMSO-ds, d): 1.48 -1.58 (HH, m), 1.75-2.05 (4H, m), (HH, m), 2.95-3.26 (4H, m), 3.46- 3.55 (5H, m), 4.62 (2H, s), 7.20 ( ÍH, d, J = 4.0Hz), 7.35-7.38. (3H, m), 7.62 (HH, d, J = 4.0Hz), 8.00 (HH, s), 10.17 (HH, s), 10.60 (HH, s) MS (ESI-): 548.2 (MH) Example 454 (2S) -N-hydroxy-2- [5- (3- (2- (benzyllaminocarbonylloxy) -acetylamino) phenyl] -2-thienyl] -3,5,5-dioxide , 6-tetrahydro-2H-thiopra-ran-2-acetamide (55 mg) NMR (DMSO-d6, d): 1.73-2.05 (4H, m), 2.37-2.46 (H, m), 2.94-3.26 (4H , m), 3.42-3.53 (ÍH, m), 4.22 (2H, d, J = 5.0Hz), 4.61 (2H, s), 7.20-7.48 (10H, m), 7.93-7.97 (2H, m), 8.84 (HH, br), 10.15 (HH, s), 10.60 (HH, s) MS (ESI-): 570.1 (MH) Example 455 (2S) -N-hydroxy-2- [1,1-dioxide] - (3- (2- (3-methylphenoxy) acetylamine) phenyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (30 mg) NMR (DMSO-ds , d): 1.73-2.06 (4H, m), 2.30 (3H, s), 2.37-2.47 (HH, m), 2.95-3.26 (4H, m), 3.40-3.50 (HH, m), 4.70 (2H , s), 6.70-6.75 (3H, m), 7.20-7.22 (2H, m), 7.38-7.40 (2H, m), 7.43 (H, d, J = 4.0Hz), 7.56 (H), d, J = 7.0Hz), 8.03 (HH, s), 8.84 (HH, s), 10.17 (HH, s), 10.60 (HH, s) MS (ESI +): 565.2 (M + H + Cl) Example 456 (2S) -N-hydroxy-2- [5- (3- (2- (3-pyridyloxy) -acetylamino) phenyl] -2-thienyl] -3,5,5-dioxide 6-tetrahydro-2H-thiopyran-2-acetamide (50 mg) NMR (DMSO-ds, d): 1.72-2.06 (4H, m), 2.37-2.48 (H, m), 2.96-3.27 (4H, m) , 3.40-3.50 (HH, m), 4.90 (2H, s), 7.20 (HH, d, J = 4.0Hz), 7.35-7.42 (3H, m), 7.52-7.56 (2M,), 7.64- 7.66 ( ÍH, m), 8.00 (ÍH, s), 8.30 (ÍH, d, J = 4.5Hz), 8.50 (ÍH, d, J = 2.0Hz), 10.30 (ÍH, s), 10.60 (1H, s) MS (ESI-) 514.1 (MH) EXAMPLE 457 (2S) -N-Hydroxy-2- [5-. {3- (2- (4-pyridyloxy) acetylamino) -phenyl} -1-dioxide. 2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (35 mg) NMR (DMSO-ds, d): 1.72-2.05 (4H, m), 2.35-2.44 (1H, m), (4H, m), 3.42-3.53 (HH, m), 5.26 (2H, s), 7.07 (2H, d, J = 7.0Hz,), 7.20 (HH, d, J = 4.0Hz), 7.40-7.42 (4H, m), 8.03 (ÍH, s), 8.41 (2H, d, J = 7.0Hz) MS (ESI +): 516.1 (M + H) Example 458 (2S) -N-hydroxy-2- [5-] 1,1-dioxide. { 3- (((2S) -2-amino-3- (4-pyridyl) -propionyl) amino) phenyl} -2-thienyl) - 3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (160 mg) L-Boc4- PiAla-OH NMR (DMSO-ds, d): 1.72-2.06 (4H, m ), 2.35-2.46 (HH, m), 2.96-3.39 (6H, m), 3.44-3.55 (HH,), 4.30 (HH, br), 7.22 (HH, d.J = 4.0Hz), 7.42-7.48 (4H, m), 7.55 (H, d, J = 6.0Hz), 7.85 (H, s), 8.39 (2H, br), 8.70 (2H, d, J = 5.5Hz), 10.60 (H, s) , 10.62 (OH, s) MS (ESI +): 529.2 (M + H) Example 459 (2S) -N-hydroxy-2- [5- (3- (((2S) -2-) 1,1-dioxide amino-3-phenylpropionyl) amino) phenyl.} -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (40 mg) from L-Boc-Fe-OH NMR (DMSO-ds, d): 1.74-2.06 (4H, m), 2.35-2.44 (HH, m), 9.95-3.27 6H,), 3.43-3.53 (HH, m), 4.15 (HH, br), 7.22 (HH, d, J = 4.0Hz), 7.25-7.35 (5H, m), 7.39-7.46 (4H, m), 7.80 (HH, s), 8.32 (2H, br), 8.85 (HH, br), 10.47 (ÍH, s). 10.73 (1H, s) MS (ESI +): 528.3 (M + H) The following compounds were obtained in a manner similar to that of Example 130. Example 460 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [3- (3- (2- (methanesulfonylamino) acetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (75 mg) NMR (DMSO-) d6, d): 1.46-1.72 (8H, m), 1.87-1.99 (2H, m), 2.06-2.24 (2H, m), 2.81-2.92 (2H, m), 3.02 (3H, s), 3.05- 3.21 (2H, m), 3.28- 3.52 (HH, m), 3.68-3.80 (HH, m), 3.98-4.06 (2H, m), 4.53, 4.87 (HH, br s), 5.94-6.08 (HH, m), 7.06-7.21 (4H, m), 7.42-7.52 (2H, m), 8.58, 8.59 (OH, br s) MS (ESI-): 598 (MH) Example 461 1, 1-dioxide (2S) ) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (phenylacetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide ( 132 mg) NMR (CDC13, d): 1.30-1.73 (8H, m), 1.84-1.97 (2H, m), 2.04-2.23 (2H, m), 2.70-2.90 (2H, m), 2.97- 3.16 ( 2H, m), 3.26-3.51 (ÍH, m), 3.63-3.73 (ÍH, m), 3.73 (2H, s), 4.52, 4.72 ( H, br s), 7.08-7.62 (12H, m), 8.68 (OH, br s) MS (ESI-): 580 (MH) Example 462 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) ) -2- (5- (3-cyclopropanecarbonylamino) phenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide 1,1-dioxide (550 mg) NMR (DMSO-d6, d): 0.72-0.89 (4H,), 1.32-1.64 (6H, m), 1.67-2.06 (5H, m), 2.34-2.49 (HH, m), 2.87-3.30 (5H, m), 3.41-3.53 (ÍH, m), 3.72-3.91 (ÍH, m), 4.44-4.75 (ÍH, s), 7.16- 7.26 (ÍH, m), 7.39-7.92 (4H, m), 8.02 ÍH, s) MS (ESI-): 531 (MH) Example 463 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- (propoxycarbonylamino) acetylamino ) phenyl.} -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopra-ran-2-acetamide (93 mg) NMR (CDC13, d): 0.93-0.99 (3H, m), 1.44 (2H, br), 1.65-1.75 (6H, m), 1.95 (2H, br), 2.04-2.26 (2H, m), 2.72-2.92 (2H, m), 3.01-3.15 (4H, m), 3.28-3.48 (ÍH, m), 3.70 (ÍH, br), 3.95-4.12 (4H, m), 1.53 (1 / 2H, s), 4.84 (1 / 2H, s), 5.54-5.64 (ÍH, m ), 7.12-7.23 (4H, m), 7.50 (HH, br, s), 7.58 (HH, s), 8.28 (HH, br), 8.70-8.78 (HH, m) MS (ESI-): 606.1 ( MH) Example 464 (2S) -N- (2-tetrahydropyranyloxy) -2- [5 (3- (2- (cyclopentyloxycarbonylamino) acetylamino) phenyl] -2-thienyl] -3,4,5-dioxide , 6-tetrahydro-2 H-thiopyran-2-acetamide (53 mg) NMR (CDCl 3, d): 1.44 (4H, br), 1.60-1.74 (4H, m), 1.86-1.96 (6H, m), 2.05-2.24 (2H, m), 2.70-2.89 (2H, m), 2.96-3.20 (4H, m), 3.29- 3.52 (HH, m), 3.64-3.75 (HH, m), 3.94-4.02 (2H, m), 4-54 (1 / 2H, s), 4.83 (1 / 2H, s), 5.16 (ÍH, br), 5.45-5.54 (ÍH, m), 7.16-7.25 (3H, m), 7.51-7.60 (2H, m), 8.30 (ÍH, br) MS (ESI- ): 632.1 (MH) The following compounds were obtained in a manner similar to that of Example 211.

Example 465 1 (1S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2- (2-oxopyrrolidinyl) acetylamino) phenyl) -2-thienyl) -3-dioxide, 4, 5, 6-tetrahydro-2H-thioprane) -2-acetamide (520 mg) NMR (DMSO-d6, d): 1.32-1.63 (6H, m), 1.68-2.09 (6H, m), 2.28 (2H, t, J = 7Hz), 2.35-2.48 (HH, m), 2.86-3.53 (6H, m), 3.46 (2H, t, J = 7Hz), 3.22- 3.40 (HH, m), 4.05 ( 2H, s), 4.44, 4.75 (ÍH, s), 7.16-7.25 (ÍH, m), 7.32-7.46 (4H, m), 8.02 (ÍH, s), 10.20 (ÍH, s), 11.25 (ÍH, s) MS (ESI-): 588 (MH) Example 466 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3 - (((3S) -N- tert- butox i carboni l - 1, 2, 3, 4-tetrahydroisoquinoline-3-carbonyl) amino) phenyl) -2-thienyl) -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (135 mg) NMR (DMSO-dg, d): 1.18-2.06 (10H, m), 1.31 (9H, s), 2.34-2.47 (1H, m), 2.88-3.31 (7H, m), 3.38-3.54 (1H,), 3.72-3.88 (ÍH, m), 4.36- 4.85 (4H, m) 7.14-7.50 (9H, m), 7.88-8.00 ( HH, m), 10.16 (HH, s), H.24 (HH, s) MS (ESI-): 722 (MH) Example 467 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) - 2- [5- (3- (oxolan-2-carbonylammo) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (670 mg) NMR (DMSO-ds, d): 1.38-1.62 (6H, m), 1.70-2.08 (7H, m), 2 14-2.78 (ÍH, m), 2.36-2.50 (ÍH, m), 2.90-3.32 (5H, m), 3.40 -3.53 (ÍH, m), 3.74-3.90 (ÍH, dd, J = 7Hz), 4.02 (ÍH, dd, J = 7Hz), 4.42 (ÍH, dd, J = 7Hz), 4.45, 4.75 (ÍH, s ), 7.19-7.25 (H, m), 7.31-7.44 (3H, m), 7.65 (H, d, J = 8Hz), 8.07 (H, s), 9.78 (H, s), 11.25 (H, s) ) MS (ESI-): 561 (MH) EXAMPLE 468 1,1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (oxolan-3-carb onyl amino) phenyl) -2-tienil] -3, 4, 5, 6- tetrah idro-2H-thiopyran-2-acetamide (700 mg) NMR (DMSO-d6, d): 1.33-1.63 (6H, m), 1.69-2.15 (4H, m), 2.09 (2H, dd, J = 8Hz) , 2.35-2.48 (HH, m), 2.86-3.32 (4H, m), 3.39-3-56 (HH, m), 3.65-3.86 (4H, m), 3.88-4.00 (HH, m), 4.45- 4.75 (ÍH, s), 7.18-7.25 (ÍH, m), 7.30- 7.52 (4H,), 8.02 (ÍH, m), 10.15 (ÍH, s), 11.24, 11.25 (ÍH, s) MS (ESI- ): 561 (MH) EXAMPLE 469 1 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- "(2- (ethyl-aminocarbonylamino) acetylamino) phenyl) -2-thienyl] -1-dioxide] - 3,, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (4.7 g) NMR (CDC13, d): 0.85-0.93 (3H, m), 1.45 (4H, br), 1.55-1.68 (2H, m ), 1.92 (2H, br), 2.01- 2.25 (2H,), 2.92-3.10 (7H, m) 3 26-3.75 (ÍH, m), 3.44-3.54 (2H, m), 3.68-4.02 (2H, m), 4.30-4.40 (ÍH, m), 4.65 (1 / 2H, br), 4.92 (1 / 2H, br), 6.02 (ÍH, br), 7.07-7.26 (7H, m), 7.54 (1 / 2H, s), 7.60 (1 / 2H, s), 9.27 (1 / 2H, s), 9.32 (1 / 2H, s) MS (ESI-): 591.2 (MH) Example 470 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- i soval eri lamino phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (200 mg) NMR (CDCl 3, d): 1.04 (6H, d, J = 6.0H ), 1.H (2H, d, J = 7.5Hz), 1.45 (2H, br) 1.65-1.75 (2H, m), 1.92-1.95 (2H, m), 2.07-2.30 (2H, m), 2.28 (2H, br), 2.30-2.40 (HH, m), 2.71-2.90 (2H, m), 3.04-3.15 (4H, m), 3.30-3.50 (HH, m), 3.64-3.75 (HH, m) , 4.52 (1 / 2H, br s), 4.82 (1 / 2H, br s), 7.20-7.30 (3H,), 7.39-7.46 (ÍH,), 7.50-7.57 (2H, m), (ÍH, m ), 8.37- 8.47 (OH,) MS (ESI-): 547.1 (MH) EXAMPLE 471 1, 1-Dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5-. { 3- (2- (metox i acetylamino) acetylamino) phenyl} -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (195 mg) NMR (CDC13, d): 1.45 (2H, br), 1.67 (4H, br), 1.97 ( 2H, br), 2.07-2.24 (2H, m), 2.80-2.87 (2H, m), 3.01-3.06 (HH, m), 3.H-3.20 (3H, m), 3.30-3.44 (HH, m ), 3.46 (3H, s), 3.68- 3.78 (HH,), 4.04 (2H, s), 4.09-4.13 (HH, m), 4.25-4.32 (HH, m), 4.53 (1 / 2H, s) , 4.84 (1 / 2H, s), 7.08-7.24 (3H, m), 7.42 (2H, br), 7.48-7.54 (2H, m), 8.56 (HI, br), 9.08 (1 / 2H, s) , 9.18 (1 / 2H, br s) MS (ESI +): 591.1 (M + H) Example 472 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- ( 2- (3-pyridi Icarboni lamino) acetylamino) phenyl} -2-thienyl] -3,4,5,6-t-tetrahydro-2H-thiopyran-2-acetamide (90 mg) NMR (CDCl 3, d) : 1.36 (2H, br), 1.65 (4H, br), 1.94 (2H, br), 2.06-2.23 (2H, m), 2.80-3.20 (7H, m), 3.55-3.72 (HI, m), 4.36 (1 / 2H, br s), 4.37-4.65 (2H, m), 4.86 (1 / 2H, s), 7.13-7.30 (5H, m) 7.43-7.49 (HI, m), 7.54 (HI, br s), 7-75-7.81 (ÍH, m), 8.23 (ÍH, d, J = 7.5Hz), 8.76 ( H, br), 9.27 (1 / 2H, s), 9.31-9.34 (HH, m), 9.40 (1 / 2H, s) MS (ESI +): 625.1 (M + H) Example 473 Obtained 1.1- (2S) -N- (2-tetrahydro-pyranyloxy) -2- [5- (3- (methoxymethylaminocarbonylamino) phenyl] dioxide} -2-thienyl) -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (100 mg) in a manner similar to that of Example 348 NMR (CDC13, d): 1.25 (2H, br), 1.43 (2H, br), 1.64 (2H, br), 1.93 (2H, br), 2.05-2.22 (2H, m), 2.70-2.88 (2H, m), 3.00-3.13 (4H, m), 3.37 ( 3H, s), 3.45-3.52 (4H, m), 4.55 (1 / 2H, br), 4.81 (1 / 2H, br), 5.40-5.49 (HI, m), 7.08-7.20 (6H, m), 7.27-7.40 (ÍH, m), 8.91 (1 / 2H, br), 8.98 (1 / 2H, br) MS (ESI-): 567.1 (M-H + NH3) Example 474 1,1-dioxide was obtained (2S) -N- (2-tetrahydro-pyranyloxy) -2- [5- (3- (2- (3-pyridylmethylamino) acetylamino) phenyl} -2-thienyl] -3,4,5, 6- tetrahydro-2H-thiopyran-2-acetamide (100 mg) in a manner similar to that of Example 249. NMR (CDCl 3, d): 1.42 (2H, br), 1.63-1.68 (4H, m), 1.95 (2H, br), 2.07-2.23 (2H, m ), 2.68- 2.95 (2H, 3.08 (2H, br s), 3.13 (2H, br), 3.27-3.44 (1H, m), 3.46 (2H, s), 3.62-3.70 (HI, m), 3.90 ( 2H, s), 4.52 (1 / 2H, br), 4.82 (1 / 2H, br), 7.24-7.34 (6H, m), 7.53-7.57 (H, m), 7.65-7.70 (2H, m), 8.57 (HH, d, J = 5.0Hz), 8.62 (1 / 2H, br), 8.65 (HH, s), 8.90 (1 / 2H, s), 9.17 (HH, d, J = 6.0Hz) MS ( ESI +): 613.2 (M + H) E j us 75 It was obtained (2S) -N- (2-tetrahydro-pyranyloxy) -2- [5- (3- (2- (tert-butylamino) 1,1-dioxide. acetylamino) phenyl.} -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (95 mg) in a manner similar to that of Example 249. NMR (CDC13, d): 1.17 (9H, s), 1.46 (2H, br), 1.65-1.70 (4H, m), 1.96 (2H, br), 2.09-2.23 (2H, m), 2.64-2.86 (2H,), 306 (2H , br s), 3.10-3.15 (2H, m), 3.36 (2H, br s), 3.43- 3.70 (2H, m), 4.53 (1 / 2H, br), 4.80 (1 / 2H, br), 7.22 -7.34 (5H, m), 7.56-7.60 (ÍH, m), 7.78 ( H, s), 9.53 (HH, s) MS (ESI-): 593.6 (M-H + NH3) The following compounds were obtained in a manner similar to that of Example 54. Example 476 2H-dioxide (2S) -N -hydroxy-2- [5- (3- (2- (N-methanesulfonylamino) -acetylamino) phenyl) -2-thienyl] -3, 4,5,6-tetrahydro-2H-thiopyran-2-acetamide (32 mg ) NMR DMSO-d6, d): 1.72-2.08 (4H, m), 2.33-2.48 (HH, m), 2.92-3.56 (7H, m), 3.00 (3H, s), 3.87 (HH, d, J) = 7Hz), 7.21 (HH, d, J = 3Hz), 7.34-7.52 (4H, m), 7.96 (HH, s), 8.84 (HH, s) MS (ESI-): 514 (MH) Example 477 1 , (2 S) -N-hydroxy-2- [5- (3-phenylacetylamino) phenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide dioxide ( 92 mg) NMR (DMSO-dg, d); 1.67-2.08 (4H, m), 2.32-2.51 (ÍH, m), (ÍH,), 3.66 (2H, s), 7.17-7.53 (ÍH, m), 8.00 (ÍH, s), 10.30 (ÍH, s), 10.60 (OH, s) MS (ESI-): 497 (MH) Example 478 (2S) -N-hydroxy-2- [5- (3- (2- (2-oxopyrrolidinyl) 1,1-dioxide ) -acetylamino) phenyl) -2-thienyl] -3, 4,5,6-tetrahydro-2H-thiopyran-2-acetamide (420 mg) NMR (DMSO-d6, d): 1.68-2.12 (6H, m) , 2.19-2.48 (3H,), 2.90-3.61 (7H, m), 4.06 (2H, s), 7.20 (ÍH, d, J = 3Hz), 7.31-7-52 (5H,), 8.02 (ÍH, s), 10.23 (OH, s), 10.62 (OH, s) MS (ESI-): 504 (MH) Example 479 (2S) -N-hydroxy-2- [5- (3 - (((3S) -1, 2, 3, 4-tetrahydro-isoquinoline-3-carbonyl) amino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetarmide (88 m) from (2S) -N- (2-tetrahydropyranyloxy-2- [5- (3- (((3S) -N-tert-butoxycarbonyl-1,2,3-dioxide, 4-tetrahydroisoquinoline-3-carbonyl) amino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide NMR (DMSO-d6, d): 1.66-2.14 (4H, m), 2.32-2.4 8 (4H, m), 2.86-3.92 (7H, m), 4.26-4.51 (3H, m), 7.12-7.52 (8H, m), 7.56-7.68 (HH, m), 8.03 (HH, s), 9.55 (HH, brs), 9.96 (HH, brs), 10.67 (HH, s), H.22 (HH, s) MS (ESI +): 540 (M + H) Example 480 1, 1-dioxide (2S) -N-hydroxy-2- [5- (3- (cyclopropan-carbonylamino) -phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (410 mg) NMR (DMSO-ds, d); 0.70-0.90 (4H, m), 1.66-2.10 (5H,), 2.34-2.49 (HH, m), 3.42-3.55 (HH, m), 7.21 (HH, d, J = 3Hz), 7.28-7.39 ( 2H, m), 7.40 (HH, d, J = 3Hz), 7.42-7.52 (HH, m), 8.01 (HH, s), 10.33 (HH, s), (HH, s) MS (ESI-): 447 (MH) EXAMPLE 481 (2S) -N-Hydroxy-2- (5- (3- (oxolane-2-ca rbonyllamino) phenyl) -2-thienyl] -3,4-dioxide, 5,6-tetrahydro-2H-thiopyran-2-acetamide (340 mg) NMR (DMSO-d6, d): 1.71-2.07 (7H,), 2.14-2.27 (H, m), 2.93-3.27 (4H, m ), 3.40-3.55 (ÍH, m), 3.84 (ÍH, dd, J = 7Hz), 4.00 (ÍH, dd, J = 7Hz), 4.41 (ÍH, d, J = 7Hz), 7.21 (ÍH, d, J = 3Hz), 7.32-7.44 (3H,), 7.65 (IH, d, J = 8Hz), 8.07 (IH, s), 8.85 (IH, s), 9.78 (IH, s), 10.60 (IH, s ) MS (ESI-): 477 (MH) Example 482 (2S) -N-hydroxy-2- [5- (3- (oxolan-3-carbonyl-lamino) -phenyl) -2-thienyl 1,1-dioxide ) -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (541 mg) NMR (DMSO-ds, d). -1.68-2.20 (4H, m), 2.09 (2H, dd, J = 8Hz), 2.24-2.49 (ÍH, m), 2.92-3.31 (4H,), 3.43-3.54 (ÍH), m), 3.65-3.76 (4H, m), 3.95 (HH, t, J = 8Hz), 7.21 (HH, d, J = 3Hz), 7.30-7.54 (4H, m), 8.02 (HH, s) , 10.17 (HH, s), 10.61 (HH, s) MS (ESI-): 477 (MH) Example 483 1, 1-dioxide (2S) -N-hydroxy-2- [5-. { 3- (2- (ethylamino carboni lamino) -acetylamino) phenyl} -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (3.0 mg) NMR (DMSO-d6, d): 1.00 (3H, t, J = 7.5Hz), 1.73- 2.05 (4H, m), 2.38-2.46 (HH, m), 2.95-3.25 (6H, m), 3.43-3.53 (HH,), 3.83, (2H, d, J = 6.0Hz), 6.10-6.18 ( 2H, m), 7-20 (HH, d, J = 4.0Hz), 7.35-7.37 (2H, m), 7.40 (HH, d, J = 4.0Hz), 7.46-7.50 (HH, m), 7.97 (HH, s), 8.84 (HH, s) MS (ESI-): 507.2 (MH) Example 484 (2S) -N-hydroxy-2- [5- (3-isovaleryl aminophenyl) 1,1-dioxide - 2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (120 mg) NMR (DMS0-d6, d): 0.95 (6H, d, J = 7.5Hz), 1.74- 2.15 (5H, m), 2.20 (2H, d, J = 7.0Hz), 2.38- 2.45 (HH, m), 2.95-3.26 (4H, m), 3.40-3.53 (HH, m), 7.20 (HH, d , J = 4.0Hz), 7.32-7.37 (2H, m), 7.46-7.50 (ÍH,), 8.00 (ÍH, s), 9.97 (ÍH, s), 10.60 (ÍH, s) MS (ESI-): 463.0 (MH) EXAMPLE 485 (2S) -N-Hydroxy-2- [5- (3- (methoxymethyl aminocarbonylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-1,1-dioxide 2H-thiopyran-2-acetamide (70 mg) NMR (DMSO- d6, d): 1.73-2.04 (4H, m), 2.35-2.45 (HH, m), 2.95-3.28 (6H, m), 3.26 (3H, s), 3.37-3.42 (HH, m), 6.24 ( ÍH, t, J = 7.0Hz), 7.16-7.27 (4H, m), 7.37 (ÍH, d, J = 4. OH z), 7.83 (OH, s), 8.67 (OH, s) MS (ESI-): 466.4 (MH) Example 486 (2S) -N-hydroxy-2- [5- (3 - (2- (3-pyridylmethyllamino) acetylamino) Phenyl] -2-thienyl] -3,4,5,6-tetrahydro-H-thiopyran-2-acetamide (60 mg) NMR (DMSO-ds, d): 1.72-2.06 (4H, m), 2.35-2.45 (HH, m), 2.97-3.28 (4H, m), 3.42-3.50 (HH, m), 3.98 (2H, br), 4.35 (2H, br), 7.22 (HH, d, J = 4.0Hz), 7.38-7.43 (2H, m), 7.48-7.52 (HH, m), 7.68-7.73 (HH, m), 7.93 (HH, s), 8.23 (HH, d, J = 7.0Hz), 8.74 (HH, d, J = 6.0Hz), 8.85 (HH, s), 9.68 (HH, br) MS (ESI-): 527.1 (MH) Example 487 1, 1-dioxide (2S) -N-hydroxy-2- [5-. {3- (2- (propoxy carbonylamino) acetylanino) phenyl} -2-thienyl) -3,4,5,6-tetrahydro -2H-thiopyran-2-acetamide (70 mg) NMR (DMSO-dg, d): 0.91 (3H, t, J = 7.0Hz), 1.58 (2H, qt, J = 7.0, 7.0Hz), 1.73-2.05 (4H, m), 2.37-2.48 (HH, m), 2.94-3.27 (4H, m), 3.44- 3.53 (HH,), 3.79 (2H, d, J = 6.0Hz), 3.93 (2H, t, J = 7.0Hz], 7.21 (ÍH, d, J = 4.0Hz), 7.35-7.42 (4H, m), 7.45-7.48 (HH, m), 7.97 (HH, s), 8.84 (HH, s), 10.08 (HH, s), 10.61 (HH, s) MS (ESI-): 522.1 (MH) Example 488 (2S) -N-hydroxy-2- [5-] 1,1-dioxide. { 3- (2- (cyclopentyloxycarbonylamino) acetylamino) phenyl} -2-thienyl) -3, 4, 5, 6-tetrahydro-2H-thiopra-ran-2-acetamide (30 mg) NMR (DMSO-ds, d): 1.50-1.70 (6H, m), 1.75-2.05 (6H, m), 2.37-2.48 (HH, m), 2.95-3.25 (4H, m), 3.43-3.53 (HH, m), 3.77 (2H, d, J = 5.0Hz), 4.97 (HH, br ), 7.20 (HH, d, J = 4.0Hz), 7.30 (HH, t, J = 7.0Hz), 7.35-7.38 (2H, m), 7.41 (HH, d, J = 4.0Hz), 7.45-7.48 (ÍH, m), 7.98 (ÍH s), 8.83 (ÍH, br), 10.07 (ÍH, s), 10.60 (ÍH, br) MS (ESI-): 548.1 (MH) Example 489 1,1-dioxide (2S) -N-hydroxy-2- [5- (3- (2- (methoxyacetylamino) phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (70 mg ) NMR (DMSO-ds, d): 1.74-2.05 (4H, m), 2.36-2.48 (HH, m), 2 95-3.26 (4H, m), 3.37 (3H, s), 3.43-3.54 (HH) , m), 3.39 (2H, s), 3.45 (2H, d, J = 6.0Hz), 7.20 (IH, d, J = 4.0Hz), 7.36- 7.40 (2H,), 7.42 (IH, d! J = 4.0Hz), 7.43- 7.48 (HH, m), 7.94 (HH, s), 8.05 (HH, t, J = 6.0Hz), 8.84 (HH, s), 10.13 (HH, s), 10.60 (HH) , s) MS (ESI-): 508.1 (MH) Example 490 (2S) -N-hydroxy-2- [5- (3- (2-1,1-dioxide) - (tert-butylamino) acetylamino) phenyl} -2-thienyl) -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (50 mg) NMR (DMSO-d6, d): 1.32 (9H, s), 1.72-2.06 (4H, m ), 2.35-2.46 (HH, m), 2.96-3.28 (4H, m), 3.38-3.52 (HH, m), 3.96 (2H, t, J = 7.0Hz), 7.22 (HH, d, J = 4.0 Hz), 7.41-7.44 (3H, m), 7.51-7.54 (HH, m), (HH, s), 8.84 (HH, br), 8.95-8.98 (2H, br) MS (ESI +): 494.1 (M + H) Example 491 1, 1-dioxide (2S) -N-hydroxy-2- [5- (3- (2- (3-pyridylcarbonylamino) acetylamino) phenyl) -2-thienyl] -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (60 mg) NMR (DMSO-d6, d): 1.72-2.04 (4H, m), 2.37-2.45 (HH, m), 2.95-3.25 (4H, m), 3-40-3.52 (HH, m), 4.00-4.06 (2H, br), 4.13 (2H, d, J = 7.0Hz), 7.20 (HH, d, J = 4.0Hz), 7.32-7.39 (2H, m), 7.42 (HH, d, J = 4.0Hz), 7.46-7.50 (HH, m), 7.59-7.64 (HH, m), 8.02 (HH, s), 8.30-8.33 ( HH, m), 8.77 (HH, d, J = 6.0Hz), 9.10 (HH, s), 9.10 (HH, t, J = 7.5Hz) MS (ESI-): 527.3 (MH) Example 492 1 was obtained , 1-dioxid of (2S) -N-hydroxy-2- [5-. { 3- (3, 3-dimethylbutyrylamino) -phenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (160 mg) from 3,3-dimethylbutyric acid of a similar to that of Example 408. NMR (DMSO-d6, d): 1.03 (9H, s), 1.66-2.10 (4H, m), 2.21 (2H, s), 2.34-2.48 (H, m), 2.92- 3.29 (4H, m), 3.42-3.56 (HH, m), 7.20 (HH, d, J = 3Hz), 7-28-7.38 (2H, m), 7.40 (HH, d, J = 3Hz), 7.45 -7.54 (HH, m), 7.99 (HH, s), 9.93 (HH, s), 10.61 (HH, s) MS (ESI-): 477 (MH) Example 493 1,1-dioxide (2S) was obtained ) -N-hydroxy-2- [5- (4-ethoxyphenyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (8.5 mg) in a manner similar to that of Example 168. NMR (DMS0-d6, d): 1-35 (3H, t, J = 7.0Hz), 1.73- 2.04 (4H,), 2.34-2.44 (ÍH, m), 2.95-3.25 (4H, m) , 3.62-3.68 (HH, m), 4.06 (2H, q, J = 7.0Rz), 6.97 (2H, d, J = 7.5Hz), 7.16 (HH, d, J = 4.0Hz), 7-33 ( HH, d, J = 4.0Hz), 7.56 (HH, d, J = 7.5Hz) MS (ESI +): 410.2 (M + H) The following compounds were obtained in a manner similar to that of Example 13 Example 494 1 (1S) -N (2-tetrahydropyranyloxy) -2- [5- (3- (cyclobutylcarbonylamino) phenyl) -2-thienyl] -3,4,5,6 -tetrahydro-2H-thiopyran-2-acetamide (340 mg) NMR (DMSO-d5, d): 1.37-1.65 (6H, m), 1.70-2.30 (10H, m), 2.37-2.46 (H, m), 2.90-3.55 (7H, m), 3.75-3.89 (ÍH,), 4.44, 4.75 (ÍH, s), 7.19-7.22 (ÍH, m), 7.34-7.40 (3H, m), 7-45- 7.51 ( HH, m), 8.03 (HH, s), 9.83 (HH, s) Example 495 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (isobutyrylaminophenyl) - 2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (330 mg) NMR (DMSO-d6, d): lH (6H, d, J = 7.0Hz), 1.36- 1.64 (6H, m), 1.70-2.05 (4H, m), 2.35-2.45 (HH, m), 2.55-2.64 (HH, m), 2.90-3.54 (6H, m), 3.75-3.90 (HH, m) , 4.45, 4.75 (H, s), 7.20-7.23 (H, m), 7.33-7.41 (3H, m), 7.45- 7.51 (H, m), 8.03 (H, s) Example 496 1, 1-dioxide of (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- (2, 2 -dime ti lpr opi oni lamino) phenyl] -2-ti enyl] -3, 4, 5, 6- tetra hydro-2H-thiopyran-2-acetamide (267 mg) NMR (DMSO-d6, d): 1.24 (9H, s), 1.36-1.64 (6H, m), 1.69-2.09 (4H, m), 2.36-2.53 (HH, m), 2.88-3.29 (4H, m), 3.30-3.51 (2H, m), 3.74-3.91 (HH, m), 4.44 (0.5H, s), 4.76 (0.5H, s), 7.19 -7.24 (HH, m), 7.30-7.42 (3H, m), 7.59-7.65 (HH, m), 8.01 (HH, s), 9.30 (HH, s) MS (ESI-): 547 (MH) Example 497 1 (1S) -N- (2-tetrahydropyranyloxy) -2- [5- (3- ((E) -2-butenoylamino) phenyl] -2-thienyl) -3,4,5-dioxide , 6-tetrahydro-2H-thiopyran-2-acetamide (160 mg) NMR (CDC13, d): 1.37-1.76 (6H, m), 1.86-2.02 (5H, m), 2.04-2.26 (2H, m), 2.68-2.94 (2H, m), 3.00-3.19 (4H, m), 3.30-3.51 (HH, m), 3.62-3.76 (HH,), 4.55 (0.5H, s), 4.83 (0.5H, s) , 6.00 (HH, dd, J = 1.5, 15Hz), 6.94-7.90 (HH,), 7.13-7.33 (4H, m), (3H, m), 8.45-8.55 (HH, m) MS (ESI-) : 531 (MH) The following compounds were obtained in a manner similar to that of Example 201. Example 498 1, 1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (-pyridyl) -2-thiyl enyl) -3,4,5,6-tetr ahi dro-2H-tiop go an-2-acetamide (60 mg) NMR (CDC13, d): 1.40-1.76 (6, m), 1.86-2.00 (2H, m), 2.06-2.25 (2H, m), 2.71-2.93 (2H, m), 3.00-3.19 (4H, m), 3.25-3.55 (HH, m), 3.60- 3.799 (HH,), (0.5H, s), 4.84 (0.5H, s), 7.16-7.35 (1H, m), 7.44-7.49 (3H, m), 8.21 (0.5H, s), 8.28 (0.5H, s), 8.59 (2H, d, J = 8Hz) MS (ESI +): 451 (M + H) Example 499 (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4- (meth i lamino carbonylmethyl) phenyl] -2-thienyl] -3,4,5,6-tetrahydro 1,1-dioxide -2H-thiopyran-2-acetamide (67 mg) MS (ESI-): 519 (MH) Example 500 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (2- (methylaminocarbonyl) -5-benzofuranyl] -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (283 mg) NMR (CDC13, d): 1.38-1.76 (6H, m) , 1.88-2.02 (2H, m), 2 04-2.25 (2H, m), 2.65-2.93 (2H, m), 3.01-3.18 (7H, m), 3.26-3.51 (ÍH,), 3.60-3.74 ( ÍH, m), 4 .55 (0.5H, s), 4.83 (0.5H, s), 6.61-6.71 (HI, m), 7.21-7.31 (2H, m), 7.43-7.50 (2H, m), 7.60-7.66 (ÍH, m), 7.83-7.88 (HH, m), 8.20 (0.5H, s), 8.27 (0.5H, s) Example 501 (2S) -N- (2-tetrahydro-pyranyloxy) 1,1-dioxide was obtained -2- (5- (4-methylthiophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (129 mg) in a manner similar to that of Example 89. NMR (CDOI3 , d): 1.38-1.76 (6H, m), 1.86-2.00 (2H, m), 2.05-2.24 (2H, m), 2.51 (3H, s), 2.61-2.90 (2H, m), 3.03-3.17 (4H, m), 3.26- 3.50 (HH, m), 3.56-3.70 (HH, m), 4.52 (0.5H, s), 4.79 (0.5H, s), 7.20-7.36 (3H, m), 7.45 - 7.54 (2H, m), 7.62-7.68 (HH, m), 7.98 (0.5H, s), 8.09-8.15 (0.5H, m) Example 502 (2S) -N- 1,1-dioxide was obtained (2-Tetrahydro-pyranyloxy) -2- [5- (4-methanesulfonyl) phenyl] -2-thienyl) -3,5,6,6-tetrahydro-2H-thiopyran-2-acetamide (57 mg) from 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- (5- (4-methylthiophenyl) -2-thienyl] -3,4,5,6,6-tetrahydro-2H-thiopyran-2-aceta measure in a manner similar to that of Preparation 1-4). NMR (CDC13, d): 1.40-1.59 (4H, m), 1.62-1.74 (2H, m), 1.88-2.02 (2H, m), 2.05-2.25 (2H, m), 2.76-2.88 (2H, m ), 3.04-3.20 (7H, m), 3.40-3.54 (HH, m), 3.60-3.77 (HH, m), 4.54 (0.5H, s), 4.82 (0.5H, s), 7.26-7.35 (HH) , m), 7.37-7.43 (HH, m), 7.73-7.80 (2H, m), 7.90-7.97 (2H, m), 8.14 (0.5H, s), 8.20 (0.5H, s) The following compounds are obtained in a manner similar to that of Example 54. Example 503 1 (1S-dioxide-2-N-hydroxy-2- [5- (4-methanesulfonyl) phenyl] -2-thienyl) -3, 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (27 mg) NMR (DMS0-d6, d): 1.72-2.10 (4H, m), 2.36-2.55 (HH, m), 2.96-3.08 (2H, m), 3.12-3.36 (5H, m), 3.39 -3.56 (ÍH,), 7.28 (ÍH, d, J = 3.9Hz), 7.70 (ÍH, d, J = 3.9Hz), 7.91 (2H, d, J = 8Hz), 7.96 (2H, d, J = 8Hz), 8.86 (OH, s) MS (ESI-): 442 (MH) Example 504 (2S) -N-hydroxy-2- [5- (4-methylaminocarbonylmethyl) -phenyl) 1,1-dioxide - 2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (25 mg) NMR (DMS0-d6, d): 1.70-2.06 (4H, m), 2.34-2.52 (1H, m), 2.59 (3H, d, J = 4.5Hz), 2.95-3.34 (4H, m), 3.36-3.54 (3H, m), 7.20 (IH, d, J = 3.9Hz), 7.29 (2H, d) , J = 8Hz), 7.43 (HH, d, J = 3.9Hz), 7.56 (HH, d, J = 8Hz), 7.94-8.02 (HH, m), 8.85 (HH, s) MS (ESI-): 435 (MH) Example 505 (2S) -N-hydroxy-2- (5- (4-pyridyl) -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran 1,1-dioxide 2-Acetamide (3.1 mg) MS (ESI +): 367 (MH) Example 506 (2S) -N-Hydroxy-2- [5- (2- (methylaminocarbonyl) -5-benzofuranyl] -2-thienyl] -3-hydrochloride , 4, 5, 6-tetrahydro-2H-thiopyran-2-acetamide (119 mg) NMR (DMSO-ds, d): 1.72-2.10 (4H, m), 2.36-2.56 (H, m), 2.81 (3H , d, J = 4.8Hz), 2.95-3.31 (4H, m), 3.40-3.55 (HH, m), 7.22 (HH, d, J = 3.9Hz), 7.49 (HH, d, J = 3.9Hz) , 7.53 (ÍH, s), 7.69 (ÍH, d, J = 8Hz), 7.75 (ÍH, d, J = 8Hz), 8.03 (ÍH, s), 8.73 (ÍH, q, J = 4.8Hz), 8.86 (HH, br s), 10.60 (HH, br, s) MS (ESI-): 461 (MH) Example 507 (2S) -N- (2-tetrahydro-pyranyloxy) -2-dioxide was obtained - [5- [4- (methansulfinyl) phenyl] -2-thienyl) -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide (45 mg) from 1,1-dioxide (2S) -N- (2-tetrahydropyranyloxy) -2- [5- (4-methylthiophenyl) -2-thienyl] -3,4,5,6-tetrahydro-2H-thiopyran-2-acetamide in a manner similar to that of Preparation 1-4). NMR (CDC13, d); 1.38-1.76 (6H, m), 1.84-2.01 (2H, m), 2.05-2.25 (2H, m), 2.77 (3H, s), 2-77-2.88 (2H, m), 3.00-3.18 (4H , m), 3.30- 3.54 (HH, m), 3.64-3.79 (HH, m), 4.53 (0.5H, s), 4.83 (0.5H, s), 7-25-7.34 (2H, m), 7.65 (2H, d, J = 8Hz), 7.70-7.78 (2H, m), 8.66 (0.5H, s), 8.71 (0.5H, s) MS (ESI-): 510 (MH) Example 508 Obtained 1, 1-dioxide (2S) -N-hydroxy-2- [5- (4- (ethansulfinyl) phenyl] -2-thienyl] -3,4,5,6,6-tetrahydro-2H-thiopyran-2-acetamide (11) mg) in a manner similar to that of Example 54. NMR (DMSO-ds, d): 1.71-2.10 (4H, m), 2.35-2.55 (HH, m), 2.78 (3H, s), 2.95-3.08 (2H, m). 3.11-3.38 (2H, m), (HH, m), 7.25 (HH, d, J = 3.9Hz), 7.61 (HH, d, J = 3.9Hz), 7.72 (2H, d, J = 8Hz), 7.85 (2H, d, J = 8H), 8.85 (1H, s) MS (ESI-): 426 (MH) fifteen 20 25

Claims (23)

REVIVAL ATIONS Compound of the formula: Rl-X-Ar- (CH2) CH2) n-R2 I) wherein R1 is lower alkyl, halogen, optionally substituted heterocyclic group or optionally substituted aryl, R2 is carboxy, protected carboxy or amidated carboxy, Ar is optionally substituted aryl or optionally substituted heterocyclic group, A is lower alkylene, X is oxa or a single bond, Y is thio, sulfinyl or sulfonyl, Z is methylene, thio, sulfinyl or sulfonyl, myn are each a number integer between 0 and 6, and l < m + n < 6, and a salt thereof. 2. Compound of claim 1, wherein the heterocyclic group of R1 and Ar are selected from the group consisting of the following (1) to (14), (1) 3 to 8 membered unsaturated heteromonocyclic group, preferably 5 or 6 members, containing between 1 to 4 nitrogen atoms, (2) 3 to 8 membered saturated heteromonocyclic group, containing 1 to 4 nitrogen atoms, (3) 3 to 8 membered unsaturated heteromonocyclic group, which contains between 1 and 2 sulfur atoms, (4) 7 to 13 membered condensed unsaturated heterocyclic group, containing 1 to 5 nitrogen atoms, (5) 3 to 8 membered unsaturated heteromonocyclic group, containing 1 or 2 atoms oxygen, (6) 3 to 8 membered saturated heteromonocyclic group, containing 1 or 2 oxygen atoms, (7) 3 to 8 membered unsaturated heteromonocyclic group, containing 1 or 2 oxygen atoms and 1 or 3 oxygen atoms nitrogen, (8) condensed unsaturated heterocyclic group of 7 a 13 members, containing 1 or 2 oxygen atoms, (9) condensed unsaturated heterocyclic group of 7 to 13 members, containing 1 or 2 sulfur atoms, (10) saturated 3 to 8 membered heteromonocyclic group, containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, (11) 7 to 13 membered unsaturated condensed heterocyclic group, containing 1 or 2 oxygen atoms and 1 or 3 nitrogen atoms, (12) 3 to 3 unsaturated heteromonocyclic group 8 members, containing 1 or 2 sulfur atoms and 1 or 3 nitrogen atoms, (13) saturated 3 to 8 membered heteromonocyclic group, containing 1 or 2 sulfur atoms and 1 or 3 nitrogen atoms, (14) 7 to 13 membered condensed unsaturated heterocyclic group, containing 1 or 2 sulfur atoms and 1 or 3 nitrogen atoms, and the aryl group of R- and Ar is Cd-C10 aryl, and, likewise, each of the heterocyclic groups mentioned above and the aryl group are optionally you are replaced by the group consisting of the following (Al) to (A35); (Al) halogen, (A2) lower alkyl, (A3) lower alkoxy, (A4) halo (lower) alkyl, (A5) halo lower alkoxy, (A6) lower alkenyl, (A7) acyl, (A8) alkylthio lower, lower alkylsulfinyl, lower alkylsulphonyl, (A9) C3-C10 aryl (AlO) C6-C10 aryl halo, (All) hydroxy, (A12) hydroxyalkyl (lower), protected lower hydroxyalkyl, (Al3) amino, ( A14) carboxy, (A15) carboxy protected, (Al 6) nitroalkenyl (lower), (A17) lower alkylenedioxy, (A18) acylamino, (Al 9) nitro, (A20) aryl of (C6-C10) alkoxy (lower) ), (A21) carbamoylalkenyl (lower) optionally N- substituted by the group consisting of lower alkyl, C6-C10 aryl, lower alkoxy-C6-C10 aryl and C6-C10 halo aryl), (A22) lower alkylaminocarbonyloxy, (A23) lower alkanoyloxy, (A24) lower alkoxy alkanoyloxy (lower), (A25) lower alkoxycarbonyloxy, (A26) lower alkenoyloxy optionally substituted by heterocyclic group of the above (1) to (14), (A27) lower cycloalkanecarbonyloxy, (A28) lower alkoxy substituted by the group consisting of carboxy, protected carboxy, lower alkanoyl, lower cycloalkanecarbamoyl, and lower alkylcarbamoyl, (A29) lower alkylcarbamoyloxy (lower) alkyl, (A30) lower alkoxycarbonylamino (lower) alkyl, (A31) aminoalkyl (lower), (A32) lower alkylcarbamoyl (lower) alkyl, (A33) heterocyclic carbonylamino, the heterocyclic group is selected from the previous ones (1) to (14) that are optionally substituted by the N-protector group, (A34) The heterocyclic groups recited previously (1) to (14) are optionally substituted by lower alkyl and (A35) oxo. 3. Compound according to claim 2, wherein R1 is lower alkyl, halogen, optionally substituted heterocyclic group consisting of the following (1) to (10); or aryl consisting of phenyl and naphthyl, R2 is carboxy, lower alkoxycarbonyl, hydroxyaminocarbonyl, tetrahydropyranyloxyaminocarbonyl or feniloalquilaminocarbonilo (lower), Ar is phenyl or heterocyclic group of the following (3) shown below, m and n are each they, an integer of 0 and 1, and m + n = lo 2, in which the heterocyclic group mentioned above is: (1) 5 or 6 membered unsaturated heteromonocyclic group, containing between 1 and 4 nitrogen atoms, (2) saturated 5 or 6 membered heteromonocyclic group, containing 1 to 4 nitrogen atoms, (3) 5 or 6 membered unsaturated heteromonocyclic group, containing 1 to 2 sulfur atoms, (4) unsaturated heterocyclic group bicyclic, 9 or 10 membered, containing 1 to 5 nitrogen atoms, (5) 5 or 6 membered unsaturated heteromonocyclic group, containing 1 to 2 oxygen atoms, (6) 5 or 6 saturated heteromonocyclic group members, which contains between 1 and 2 oxygen atoms, (7) 5 or 6 membered unsaturated heteromonocyclic group, containing between 1 and 2 oxygen atoms and between 1 and 3 nitrogen atoms, (8) 9 or 10-membered bicyclic unsaturated heterocyclic group, containing 1 to 2 oxygen atoms, (9) 9 or 10 membered bicyclic unsaturated heterocyclic group, containing 1 to 2 sulfur atoms, (10) 5 or 6 membered saturated heteromonocyclic group, containing between 1 and 2 oxygen atoms and between 1 and 3 nitrogen atoms, in which the heterocyclic group is optionally substituted by the group consisting of the following (Bl) a (B8) ): (Bl) lower alkanoyl, (B2) lower alkyl, (B3) lower alkoxy, (B4) lower alkoxycarbonylamino, (B5) carbamoyl or lower alkylcarbamoyl, (B6) lower alkoxycarbonyl, (B7) halo, and (B8) oxo; and the aforementioned aryl is optionally substituted by the group consisting of (A l) to (A 35) according to claim 2. 4. Compound according to claim 3, wherein a group of the formula : rX It is one of the following formulas R1 is lower alkyl, halogen, optionally substituted heterocyclic group consisting of the following (1) to (10); or aryl consisting of phenyl and naphthyl, R2 is carboxy, lower alkoxycarbonyl, hydroxyaminocarbonyl, or tetrahidropirani Loxi-aminocarbonyl, Ar is phenyl or heterocyclic group according to (3) shown below, m and n are each a number integer of 0 or 1, and m + n = I 2, in which the above-mentioned heterocyclic group is (1) pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, pyridyl N-oxide, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl, tetrazolyl, dihydrotriazinyl, (2) azetidinyl, pyrrolidinyl, imidazolidinyl, piperidinyl, piperidino, pyrazolidinyl, piperazinyl, (3) thienyl; (4) indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, tetrahydroisoquinolyl, indazolyl, benzot r i iazol it, azo tetr lopi r idi it, tetrazolopyridazinyl, dihidrotriazolo- pyridazinyl, (5) furyl, (6) oxolanyl, (7 ) oxazolyl, isoxazolyl, oxadiazolyl, (8) benzofuranyl, benzodihidrofuranilo, benzodioxolenilo, (9) benzothienyl, dihydrobenzothienyl, (10) morpholinyl, morpholino, wherein the heterocyclic group may be optionally substituted by the group consisting of (Bl) to ( B8), as defined in claim 3, and the aforementioned aryl is optionally substituted by the group consisting of the following (l) a (A 34), (Al) halogen, (A2) lower alkyl, (A3) ) lower alkoxy, (A4) haloalkyl (lower), (A5) haloalkoxy (lower), (A6) lower alkenyl, (A7) acyl, (A8) lower alkylthio, lower alkylsulfinyl, lower alkylsulonyl, (A9) C6-C10 aryl (AlO) haloaryl (C6-C10) ), (All) hydroxy, (A12) hydroxyalkyl (lower), or hydroxy lower protected alkyl, (Al 3) amino, (Al 4) carboxy, (A15) carboxy protected, (A16) nitro alkenyl (lower), (A17) ) lower alkylenedioxy, (Al 8) acylamino, (Al 9) nitro, (A20) aryl of (C-C10) alkoxy (lower), (A21) carbamoylalkenyl (lower) optionally N- substituted by the group consisting of lower alkyl, C6-C10 aryl, C6-C10 lower alkoxy-aryl, and C6-C10 aryl halo), (A22) lower alkylaminocarbonyloxy, (A23) lower alkanoyloxy, (A24) lower alkoxy (lower) alkanoyloxy, (A25) lower alkoxycarbonyloxy, (A26) lower alkenoyloxy optionally substituted by the above heterocyclic group (1), (A27) lower cycloalkanecarbonyloxy, (A28) lower alkoxy substituted by the group consisting of carboxy, protected carboxy, lower alkanoyl, cycloalkanecarbamoyl lower, and lower alkylcarbamoyl, (A29) lower alkylcarbamoyloxy lower alkyl, (A30) lower alkoxycarbonylamino lower alkyl, (A31) aminoalkyl (lower), (A32) lower alkylcarbamoyl lower alkyl, (A33) heterocyclic carbonylamino, the heterocyclic group is selected from the above (2), (4) and (5) which are optionally substituted by the N-protecting group, (A34) the above-mentioned heterocyclic group (7) is optionally substituted by lower alkyl. 5. Compound according to claim 4, which has the following formula: in which a group of the formula: It is one of the following formulas: R1 is lower alkyl, phenyl, halophenyl or (halo) (phenyl) phenyl, R2 is carboxy or hydroxyaminocarbonyl, and y n are each an integer of 0 or 1, and m + n = l. 6. Compound according to claim 4, having the following formula: in which a group of the formula: It is one of the following formulas R2 is carboxy or hydroxyaminocarbonyl, m and n are each an integer of 0 or 1, and m + n = l R1 is halogen; heterocyclic group consisting of pyridyl, thienyl, furyl, benzofuranyl or benzothienyl, wherein the heterocyclic group is optionally substituted by the group consisting of lower alkanoyl, lower alkyl, lower alkoxy, lower alkoxycarbonylamino and lower alkylcarbamoyl; naphthyl or phenyl which is optionally substituted by the group consisting of the following (Cl) to (C31); (Cl) halogen, (C2) lower alkyl, (C3) lower alkoxy, (C4) lower haloalkyl, (C5) lower haloalkoxy, (C6) lower alkenyl, (C7) lower alkylcarbamoyl, carbamoyl, phenyl lower alkylcarbamoyl, alkanoyl lower, (C8) lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, (C9) phenyl, naphthyl, (CIO) halophenyl, (Cll) hydroxyl, (C12) mono- or dihydroxyalkyl (lower), phenoxycarbonyloxy (lower) alkyl, (C13) amino), (C14) carboxyl, (C15) lower alkylenedioxy, (C16) lower alkanoylamino, phenylalkanoylamino (lower), halophenylalkanoylamino (lower), lower alkoxy-alkanoylamino (lower), lower alkoxy-alkanoylamino (lower), phenoxyalkanoy-lamino (lower), lower alkoxyphenoxy alkanoylamino (lower), lower alkyl-alkanoylamino (lower) alkanoylamino, halofenoxi-alkanoylamino (lower), carboxyalkanoylamino (lower), lower alkoxycarbonyl-alkanoylamino (lower), lower alkylcarbamoyl-alk nolamino (lower), haloalkanoylamino (lower), lower alkenyl alkanoylamino (lower), lower alkoxy alkanoylamino (lower), phenylalkoxy (lower) alkanoyl amino (lower), piperidinyloxyalkanoylamino (lower), N-alkoxycarbonylpiperidinyloxy lower alkanoyl amino (lower) , pyridyloxyalkanoylamino (lower), hydroxyalkanoylamino (lower), lower alkanoyloxy alkanoylamino (lower), lower alkylcarbamoyloxy-alkanoylamino (lower), N, N-di (lower alkyl) carbamoyloxy, piperidinocarbonyloxyalkanoylamino (lower), f- phenylalkylcarbamoyloxy (lower) alkanoy lamino (lower ), lower alkoxycarbonylamino (lower) alkanoylamino, aminoalkanoylamino (lower), lower alkoxycarbonylamino (lower) alkanoylamino, f-lorenylmethoxycarboni-1-aminoalkanoylamino (lower), lower alkylamino-alkanoylamino (lower), [N, N-di (lower alkyl) amino] alkanoylamino (lower), [N-alkyl] lower-N- (lower alkoxycarbonyl) amino] alkanoylamino (lower), [N-lower alkyl-N- (f-luorenylmethoxycarbonyl) amino] -alkanoylamino (lower), [N-alkyl] Lower-N- (mono- or dialkylcarbamoyl (lower)) amino] alkanoylamino (lower), [N- (mono- or di (lower alkyl) carbamoyl) ^^ amino] alkanoylamino (lower), benzoylamino-alkanoylamino (lower), lower alkanoylamino 20 alkanoylamino (lower), lower alkanesulfonylamino alkanoylamino (lower), lower alkoxy alkanoylamino (lower) alkanoylamino (lower), cycloalkyloxycarbonylamino (lower) alkanoylamino (lower), 25-pyridylcarbonylamino (lower) pyridylcarbonylaminoalkanoylamino (lower), phenylalkoxycarbonylamino (lower) alkanoylamino (lower), lower alkoxyphenylsulfonylamino (lower) alkanoylamino, lower hydroxyalkylamino (lower) alkanoylamino, morpholinoalkanoylamino (lower), oxooxazolidinylalkanoylamino (lower), oxopyrrolidynylalkanoylamino (lower) , trimethylhydantoinylalkanoylamino (lower), lower alkenylamino alkanoylamino (lower), lower alkoxy lower alkylamino (lower) alkanoylamino, phenylalkylamino (lower) alkanoylamino (lower), pyridylalkylamino (lower) alkanoylamino 15 (lower), lower alkoxycarbonylamino, phenylalkoxycarbonylamino (lower) lower alkoxy alkoxycarbonylamino (lower), ^^ haloalkoxycarbonylamino (lower), aminoalkoxycarbonylamino (lower), 20 f talimidoalkoxycarbonylamino (lower), carbamoylamino, (mono- or dialkyl lower) carbamoi lamino, naf ti Icarb amo ilamino, halof eni Icarbamoyl amino, alkoxy phenylcarbamoylamino, alkenylcarbamoylamino 25 lower, (lower) cycloalkylcarbamoylamino (lower), phenylalkylcarbamoylamino (lower), haloalkylcarbamoylamino (lower), lower alkoxy alkylcarbamoylamino (lower), hydroxyalkylcarbamoylamino (lower), (lower alkyl) (diphenyl) silyloxyalkyl carbamoylamino (lower), carboxyalkylcarbamoylamino (lower), lower alkoxycarbonyl lower alkylcarbamoylamino (lower), lower alkylcarbamoyl lower alkylcarbamoylamino, or pyridylcarbamoylamino, lower alkylsulfonylamino, lower alkenylamino, lower cycloalkancarbonylamino , lower alkenyloxycarbonylamino, f-enoxycarbonylamino, lower alkylthiocarbonylamino, (C17) phenylalkoxy (lower), (C18) lower alkenyl, mono- or di (lower alkyl) carbamoylalkenyl (lower), (2- (methylcarbamoyl) ethenyl, 2- (ethylcarbamoyl) ) ethenyl, 2- (propylcarbamoyl) ethenyl, 2- (isopropylcarbamoyl) ethenyl, 2- (dimethylcarbamoyl) ethenyl, f-enylcarbaryl-alkenyl (lower), alkoxycarbamoyl lower alkenyl (lower), halophenylcarbamoylalkenyl (lower), (C19) alkylaminocarbonyloxy lower, (C20) lower alkanoyloxy, (C21) lower alkoxy alkanoyloxy (lower), (C22) lower alkoxycarbonyloxy, (C23) pyridylalkenoyloxy (lower), (C24) lower cycloalkancarbonyloxy, (C25) carboxyalkoxy (lower), lower alkoxycarbonyl lower alkoxy, lower alkanoyl lower alkoxy, lower cycloalkancarbamoyl lower alkoxy, lower alkylcarbamoyl lower alkoxy, (C26) ) lower alkylcarbamoyloxy (lower) alkyl, (C27) lower alkoxycarbonylamino lower alkyl, (C28) aminoalkyl (lower), (C29) lower alkylcarbamoyl lower alkyl, (C30) furylcarbonylamino, teretahydroisoquinolylcarbonylamino, N-lower alkoxycarbonyl- teretahydroisoquinolylcarbonylamino, pyrrolidiniumcarbonyllamino, (C31) oxazolyl, lower alkylazoadiazolyl. 7. Compound according to claim 6, wherein a group of the formula: e the following formulas: R2 is hydroxyaminocarbonyl, m is 0 and n is 1, a group of the formula: ; 1X is the group of the following formulas (a) to (e); (to) to R1 is halo, naphthyl, phenyl, mono- or dihalophenyl, mono- or di-alkylphenyl (lower), lower alkoxyphenyl, tri- halo at 1 qui 1 f in i 1 o (lower), trih 1 or 1 coxif in i 1 or (lower), alkenylphenyloinferior r, a 1 qu i 1 carb i i f i1 i or lower, carbamoyl phenyl, f enylalkylcarbamoylfyl (lower), lower alkanoyl phenyl, lower alkyl, at 1 qui 1 its 1 fini 1 1 or less, lower alkylsulfonylphenyl, phenylphenyl, (halo) (phenyl) phenyl, halofenylfyl, hydroxyphenyl, mono- or dihydroxy alkylphenyl (lower), f-enoxycarbonyloxyalkylphenyl (lower), Amino acid, carboxymethyl, lower alkylenedioxyphenyl, canosul fonyl amino pheni lower, ^^ a 1 queno i

1 - ami no f on i 1 or lower, cycloalkane carboni lamino phenyl lower, Phenylalkoxyphenyl (lower), mono- or di (lower alkyl) carbamoylalkenylphenyl (lower), phenylcarbamoylalkenylfyl (lower), alkoxycarbamoyl lower than l qu in i l f l i l (i n f e r i o r), Halofenylcarbamoylalkenylfenyl (lower), lower alkylcarbamoyl, lower alkanoyloxyphenyl, lower alkoxy alkanoyloxyphenyl (lower), lower alkoxycarbonylsiloxyphenyl, pyridylalkenoyloxyphenyl (lower), cycloalkylcarbonylsiloxyphenyl (lower), caboxy 1 cox if in i 1 (lower), lower alkoxycarbonyl lower alkoxyphenyl, lower alkanoyl lower alkoxyphenyl, lower cycloalkanecarbamoyl lower alkoxyphenyl, lower alkylcarbamoyl lower alkoxyphenyl, lower alkylcarbamoyloxy lower alkylphenyl, lower alkoxycarbonylamino 15 alkylphenyl (lower), amino alkylphenyl (lower), alkylcarbamoyl lower than l qu i l f e n i l o (i n f e r i o r), ^^ f ur i lcarboni lammof eni lo, 1,2, 3, 4- teret ahidro i so qui nol i Icarboni lamino feni lo, N-t-butoxycarbonyl, 1, 2, 3, 4-teretahydroisoquinolyl-carbonyl-aminophenyl, pyrrolidinylcarbonylaminophenyl, oxazolyl phenyl, alkyloxadiazolyl phenyl lower, R12 is lower alkyl optionally substituted by the group consisting of phenyl, halophenyl, lower alkoxyphenyl, lower alkoxy, phenoxy, lower alkoxy phenoxy, halofenoxy, lower alkylphenoxy, carboxy, lower alkoxycarbonyl, lower alkylcarbamoyl, halo, lower alkenyloxy, lower alkoxy, alkoxy (lower), phenylalkoxy (lower), p ip eridini 1 oxy, N-lower alkoxycarbonyl piperidinyloxy, pyridyloxy, hydroxy, lower alkanoyloxy, mono- or dialkylcarbamoyloxy (lower), piperidinylcarbonyloxy, phenyalkylcarbamoyloxy (lower), lower alkoxycarbonylamino, amino, alkoxy carbonylamino lower, fluorenylmethoxycarbonylamino, mono- or dialkylamino (lower), N-lower alkyl-N- (lower alkoxycarbonyl) amino, N-lower alkyl-N- (fluorenylmethoxycarbonyl) amino, N-lower alkyl-N- (mono- or dialkylcarbamoyl (lower)) amino, N- (mono- or di (lower alkyl) carbamoyl) amino, benzoylamino, lower alkanoylamino, alkanesulfonylamino lower, lower alkoxy alkanoylamino (lower), alkyloxycarbonylamino (lower) cycle, pyridyl Icarboni lamino, morpholinocarbonyl-amino, phenylalkoxy-oxycarbonylamino (lower), lower alkoxy f enylsulphonylamino lower, hydroxy alkylamino (lower), morpholino, oxooxazolidinyl, oxopyr rol idini lo, trimethylhydantoinyl, pyridyl, lower alkenylamino, lower alkoxy lower alkylamino, phenylalkylamino (lower), pyridylamino lamino (lower) ), and cycloalkyl (lower), M is oxygen or sulfur, R13 is lower alkyl, phenylalkyl (lower), lower alkoxy (lower) alkyl, haloalkyl (lower), aminoalkyl (lower), or phthalimidoalkoxycarbonylamino (lower), lower alkenyl, phenyl, R 1 S is hydrogen or lower alkyl, R 14 is hydrogen, lower alkyl, naphthyl, halophenyl, lower alkoxyphenyl, lower alkenyl, lower alkyl cycloalyl (lower), phenylalkyl (lower), haloalkyl (lower), lower alkoxy (lower) alkyl, hydroxyalkyl (lower), (lower alkyl) (diphenyl) silyloxy (lower) alkyl, carboxyalkyl (lower), lower alkyl alkoxycarbonyl (lower), lower alkylcarbamoyl (lower) alkyl, or pyridyl, wherein R16 is benzothienyl, benzofuranyl, thienyl, furyl, lower alkylpyridyl, pyridyl, lower alkoxypyridyl, lower alkoxycarbonylaminopyridyl, lower alkanoylthienyl, lower alkylcarbamoylbenzofuranyl. 8. Compound according to claim 7, wherein a group of the formula: is the same group as (a), (c), (d) and (e) of claim 7, and the following formula (b): wherein R12 is lower alkyl, phenylalkyl (lower), halophenyl (lower) alkyl, lower alkoxyphenyl (lower) alkyl, lower alkoxy (lower) alkyl, phenoxyalkyl (lower), lower alkoxyphenoxy (lower) alkyl, halofenoxy (lower) alkyl , lower alkylphenoxy lower alkyl, carboxyalkyl lower, lower alkoxycarbonyl lower alkyl, lower alkylcarbamoyl lower alkyl, haloalkyl lower, lower alkenyloxy lower alkyl, lower alkoxy lower alkoxy lower alkyl, phenyl-lower alkoxy (lower) alkyl, piperidiniloxialquilo (lower), Nt-butoxicarbonilpiperidiniloxi (lower) alkyl, pyridyloxyalkyl (lower) alkyl, hydroxy (lower), lower alkanoyloxy alkyl (lower) alkyl, mono- or dialkylcarbamoyloxy (lower) alkyl (lower) piperidinilcarboniloxi - alkyl (lower), phenylalkylcarba oxyloxy (lower) alkyl (lower), alkoxycarbonylamino lower alkyl (lower), aminoalkyl (lower), lower alkoxycarbonylamino (lower) alkyl, f-luorenylmethoxycarbonylamino-lower alkyl, mono- or dialkylamino (lower) alkyl (lower), N-lower alkyl-N- (lower alkoxycarbonyl) aminoalkyl (lower ), N-lower alkyl- N- (f-luorenylmethoxycarbonyl) aminoalkyl 10 (lower), N-lower alkyl-N- (mono- or dialkylcarbamoyl (lower)) aminoalkyl (lower), N- (mono- or di (lower alkyl) carbamoyl) aminoalkyl (lower), benzoi 1 ainoa 1 qu i 1 or (lower), 15 alkanoylamino lower alkyl (lower), lower alkanesulfonylamino lower alkyl, lower alkoxy alkanoylamino (lower) alkyl (lower), cycloalkyloxycarbonylamino (lower) 20 alkyl (lower) amino piridilcarbonil- to qui it (in ferior), morfolincarbonilaminoalquilo (lower) fenilalcoxioxicarbonilamino (lower) alkyl (lower) lower alcoxifenilsulfonilamino alkyl (lower), hydroxyalkylamino (lower) alkyl (lower), morpholino (lower ), oxooxazo 1 Idini 1 to qui the (lower) oxopirro 1 Idini 1 to qui the (lower) trimetilhidantoinilalquilo (lower), pyridyl (lower), lower alkenylamino alkyl (lower) alkylamino lower alkoxy (lower) alkyl (lower ), Phenylalkylamino (lower) alkyl (lower), pyridylalkylamino (lower) alkyl (lower), cycloalkyl (lower), (amino) (phenyl) alkylamino (lower), (lower alkoxycarbonylamino) (phenyl) alkyl (lower), pyridyloxyalkyl (lower), hydroxyalkyl (lower), ^ lower alkanoyloxy (lower) alkyl, mono- or dialkyl-carbamoyloxy (lower) alkyl (lower), piperidinylca riloiloxy 20 alkyl (lower) fenilalquilcarbamoiloxi (lower) alkyl (lower), lower alkoxycarbonylamino alkyl (lower) alkylamino (lower), lower alkoxycarbonylamino alkyl (lower) luorenilmetoxicarbonilamino f (lower) alkyl, mono- or dialkylamino (lower) alkyl ( lower), N-lower alkyl-N- (lower alkoxycarbonyl) aminoalkyl (lower), N-lower alkyl- N- (f-lorenylmethoxycarbonyl) aminoalkyl (lower), N-lower alkyl-N- (mono- or di (alkylcarbamoyl) (lower)) aminoalkyl (lower), N- (mono- or di (lower alkyl)) 10 carbamo i 1) aminoal qui lo (lower), benzoylamino (lower) alkyl, lower alkanoylamino (lower) alkyl, lower alkanesulfonylamino (lower) alkyl, lower alkanoylamino (alkoxy) 15 (lower) alkyl (lower), ci cloal qui loxi carbon i lamino (lower) ^ P (lower) alkyl, pyridylcarbonylamino (lower) alkyl, (lower) alkyl morpholinocarbonylamino, f enilalcoxioxicar- 20 bonilamino (erior inf) alkyl (lower) lower enilsulfonilamino alcoxif alkyl (lower), hydroxyalkylamino (lower) alkyl (lower) morpholino (lower) oxooxa zo 1 Idini 1 alqui the (lower) oxopi r ro 1 Idini 1 to qui the (lower) trimetilhidantoinilalquilo (lower), pyridyl (lower), lower alkenylamino alkyl (lower), lower alkoxy alkylamino ( lower) alkyl (lower), phenylalkylamino (lower) alkyl (lower), pyridylalkylamino (lower) alkyl (lower), cycloalkyl (lower), (amino) 10 (f in i 1 o) to 1 qu i 1 amino (lower), (lower alkoxycarbonylamino) (phenyl) lower alkyl, (amino) (lower alkoxy) lower alkyl, (lower alkoxycarbonylamino) (lower alkoxy) I rent 15 (lower), (amino) (carboxy) alkyl (lower), (lower alkoxycarbonylamino) ^ P (carboxy) alkyl (lower), (amino) (lower alkoxycarbonyl) lower alkyl, (lower alkoxycarbonylamino) 20 (lower alkoxycarbonyl) - at 1 qui (lower), (amino) (phenylalkoxy (lower)) - lower alkyl, (lower alkoxycarbonylamino) (phenylalkoxy (lower)) lower alkyl, (amino) ) (pir id 1) alkyl (lower), (lower alkoxycarbonylamino) (pyridyl) lower alkyl, (amino) (hydroxy) lower alkyl, lower alkoxycarbonylamino (hydroxy) lower alkyl, (amino) (amino) to qui 1 (lower), (lower alkoxycarbonylamino) (amino) lower alkyl, (amino) (lower alkoxycarbonylamino) lower alkyl, lower alkoxycarbonylamino (lower alkoxycarbonylamino) alkyl (lower), (amino) (lower cycloalkane) lower alkyl, lower alkoxycarbonylamino (lower cycloalkane) lower alkyl. 9. Compound according to claim 7, to a group of the formula: ; X is the group of the following formulas (a) to (e) (a) Rll- // W in which R11 is bromine, 2-naphthyl, phenyl, 3 (or 4) -chlorophenyl, 2 (or 3 or 4) -fluophenyl, 3,4-dichlorophenyl, 3,5-difluophenyl, 3 ( or 4) -methylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 4- (t-butyl) phenyl, 3,4-dimethylphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-trifluoromethylphenyl, 4-trifluoromethoxyphenyl, 4-ethenylphenyl, -methylcarbamoylphenyl, 4-ethylcarbamoylphenyl, 4-carbamoylphenyl, 4-10-benzylcarbamoylphenyl, 4-acetylphenyl, 4-methylthiophenyl, 4-ethylthiophenyl, 4-methylsulfinylphenyl, 4-methylsulfonylphenyl, phenylphenyl, 4-phenyl-3-fluophenyl, 4- (4 - fluophenyl) phenyl, 3 (or 4) -hydroxyphenyl, 3 (or 15 4) -hi droxime ti 1 f eni 1 o, 4- (l, 2-dihydroxyethyl) phenyl, 4 - ^ fc (phenoxycarbonyloxymethyl) phenyl, 3 (or 4) -aminophenyl, 4-carboxyphenyl, 3,4- methylenedioxyphenyl, 4- (methanesulfonylamino) 20 phenyl, 3- (2-butenoylazino) phenyl, 3- (cyclopropanecarbonylamino) phenyl, 3- (cyclobutanecarbonylamino) phenyl, 3- (cyclopentanecarbonylamino) phenyl, 4-benzyloxyfine, 4- (2- (methylcarbamoyl) Ethenyl) phenyl, 4- (2- (methylcarbamoyl) ethenyl) phenyl, 4- (2- (propylcarbamoyl) ethenyl) phenyl, 4- (2- (isopropylcarbamoyl) ethenyl) phenyl, 4-2- (dimethylcarbamoyl) ethenyl) phenyl, 4- (2- (f -enylcarbamoyl) ethenyl) phenyl, 4- (

2- (methoxy-

3-enylcarbamoyl) ethenyl) phenyl, 4- (2- (4- fluofenylcarbamoyl) ethenyl) phenyl, 4- (methylaminocarbonyloxy) phenyl, 4 - (eti 1 ami no ca rbon i 1 ox i) phenyl 1 or, 4-propanoyloxyphenyl, 4- (methoxyacetyloxy) phenyl,

4- (ethoxycarbonyloxy) phenyl, 4- (3- (3-pyridyl) acryloyloxy) phenyl, 4 - (cyclopropylcarbonyloxy) phenyl, 4 - (ca rb oxi me toxi) phenyl, 4 - (ethoxycarbonylmethoxy) phenyl, 4- ( t-15 bu t oxocarboni 1 me toxi) f in i 1, 4- (propanoi lmetoxi) f eni lo, 4 - ^^ (cyclopropylcarbamoylmethoxy) phenyl, 3 (or 4) - (me ti 1 ca rb master i lme toxi) f on i 1, 4- (eti 1 carb amo i lme toxi) feni 1 o, 4- 20 (propylcarbamoylmethoxy) phenyl, 3 (or 4) - (me ti lcarbamoi loxime t il) phenyl, 4- (methoxycarbonylaminomethyl) phenyl, 4- (t-butoxycarboni laminomethyl) 1) phenyl, 4- aminomethylphenyl, 4- (methylcarbamoylmethyl) Phenyl, 3- (2- (or 3) -furylcarbonylamino) phenyl, 3- (1, 2, 3, 4-teretahydroisoquinol and Icarboni lamino) phenyl, 3- (N- (t-butoxycarbonyl) -1,2, 3,4-teretahydroisoquinolylcarbonylamino) phenyl, 3- (pyrrolidinylcarbonylamino) phenyl, 4- (1, 3-oxazolyl) phenyl, 4- (

5-methyl-1,2,4-oxadiazol-3-yl) phenyl, wherein R 12 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, neopentyl, phenylmethyl, 4-chlorofinylmethyl, 4-methylphenylmethyl, methoxymethyl, ethoxymethyl, propoxymethyl, butoxymethyl, isopropyloxymethyl, 1-methoxyethyl, 2-? t? ethoxyethyl, phenoxymethyl, 2-phenoxyethyl, 3 (or 4) -methoxyphenoxymethyl, 4-fluo (or chloro) phenoxymethyl, 3 (or ) -methylf-enoxymethyl, 2-carboxyethyl, 2-methoxycarbonylethyl, 2-t-butoxycarbonylethyl, 2-methylcarbamoylethyl, 2-chloroethyl, chloromethyl, allyloxymethyl, (2-ethoxyethoxy) methyl, benzyloxymethyl, 4-piperidinyloxymethyl, (Nt-butoxycarbonyl-4) - piperidinyl) oxymethyl, 3 (or 4) -pyridyloxymethyl, hydroxymethyl, 2-hydroxyethyl, acetoxymethyl, 1-acetoxyethyl, methylcarbamoyloxymethyl, 1- (N-methyl-N-ethylcarbamoyloxy) methyl, (piperidin-carbonyloxy) methyl, (benzylcarbamoyloxy) methyl, (t-butoxycarbonylamino) methyl, aminomethyl, 1-aminoethyl, 1- (t-butoxycarbonylamino) ethyl, 2-aminoethyl, methoxycarbonylaminomethyl, 2- (methoxycarbonylamino) ethyl, ethoxycarbonyl-10-aminomethyl, propoxycarbonylaminomethyl, 1- (f-luorenyl-methoxycarbonylamino) methyl, 2- (t-butoxycarbonylamino) ethyl, 2 - (f luorenylmethoxycarbonylamino) ethyl, 1-aminoisopropyl, 1-aminopropyl, 1- (t-butoxycarbonyl) propyl, 15 1- (t-butoxycarbonylamino) isopropyl, 1,5-diaminopentyl, 1,5-bis (t-butoxy- ^^ carbonylamino) pentyl, methylaminomethyl, ethylaminomethyl, 3- (2- (N-methyl-N-ethylamin) methyl, 3- (dimethylamino) methyl, 3- 20 (pentylamin) methyl, 3- (t-butylamino) methyl, 3- (3-me ti 1 amine ti 1 o, 3 - (2 - (N-me ti 1 - N-methoxycarbonylamino) methyl, 1- (N-methyl-Nt-butoxycarbonylamino) ethyl, 1- (N-ethyl-Nt-butoxycarbonylamino) methyl, 2- (N-methyl-N- 25 (f-luorenylmethoxycarbonyl) amin) - ethyl, 2- (N-methyl-N- (t-butoxycarbonyl) amin) ethyl, 1- (N-methyl-N- (dimethylcarbamoyl) amino) methyl, 1- (dimethylcarbamoylamino) methyl, 1- (N- (ethylcarbamoyl) amino) methyl, 2- (N- (ethylcarbamoyl) amino) ethyl, benzoylaminomethyl, 2-benzyl-1-aminoethyl, acetylaminomethyl, isobutyrylaminomethyl, pivaloylaminomethyl, 1- (methanesulfonylamino) methyl, 2- (methanesulphonylamino) ethyl, methoxyacetylaminomethyl, Cyclopentyloxycarbonylaminomethyl, pyridylcarbonylaminomethyl, morpholinocarbonylamino-methyl, benzyloxycarbonylaminomethyl, l- (4-methoxy-fsylsulfonylamino) methyl, 1- (2-hydroxyethylamino) methyl, morpholinomethyl, 1- (2-15-oxo-1,3-oxazolidin-1) il) methyl, 1- (2-oxopyrrolidin-1-yl) methyl, 1- (3,4,4- ^^ trimethylhydantoin-1-yl) ethyl, allylaminomethyl, 1- (2-ethoxyethylamino) methyl, benzylaminomethyl, - (3-pyridylmethylamino) methyl, 2-phenyl-1-20-aminoethyl, 1-amino-1-phenylmethyl, 1-t-butoxycarbonylamino-1-p-enylmethyl, 1-amino-2-phenylethyl, 1-t-butoxycarboni lamino -2- phenylethyl, l-amino-2-methoxyethyl, 1-t-butoxycarbonylamino-2-metoxietyl, l-amino-3-25 carboxypropyl, lt-butoxycarbonylamino-3-carboxypropyl, l-amino-3- (t -butoxycarbonyl) propyl, 1-t-butoxycarbon and lamino-3-t-butoxycarbonylpropyl, etc. ), l-amino-2-benzyloxyethyl, lt-butoxycarbonylamino-2-benzyloxyaminoethyl, l-amino-2- (3-pyridyl) ethyl, lt-butoxycarbonylamino-2- (3-pyridyl) ethyl, l-amino-2- (4-pyridyl) ethyl, 1-t-butoxycarbonylamino-2- (4-pyridyl) ethyl, 1-amino-2-hydroxyethyl, 1-t-butyloxycarbonylamino-2-hydroxyethyl, (1,5-diamino) pentyl, 1-t-butoxycarbonylamino-5-aminopentyl, 1,5-bis (t-butoxycarbonylamino) pentyl, l-amino-2- (t-butoxycarbonylamino) pentyl, l-amino-2-cyclohexylethyl, 1-t-butoxy carboni lamino -2- cyclohexylethyl, wherein M = 0 and R13 is methyl, ethyl, propyl, isopropyl, benzyl, 2-methoxyethyl, 2-chloroethyl, 2-aminoethyl, 2-phthalimidoethyl, allyl, phenyl, or M = S and R13 is methyl, ethyl, wherein R15 is hydrogen and R14 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, 1-naphthyl, 3 (or 4) -chlorophenyl, 3-methoxyphenyl, allyl, cyclohexylmethyl, benzyl, chloroethyl, methoxymethyl, 2-methoxyethyl, 2-hydroxyethyl, 2- ((t-butyl) (diphenyl) silyloxy) ethyl, carboxymethyl, ethoxycarbonylmethyl, methylcarbamoylmethyl, or 3-pyridyl, R14 is ethyl and R15 is methyl, // \ R16 wherein R16 is 2-benzothienyl, 2-benzofuranyl, 2 (or 3) -thienyl, 2-furyl, 3-pyridyl, l-methyl-4-pyridyl,

6-methyl-3-pyridyl, 6-methoxy-3 - pyridyl, 5-methoxycarbonylamino-3-pyridyl, 5-acetyl-2-thienyl, 2-methylcarbamoyl-5-benzofuranyl. 10. Process for the preparation of a compound of the formula: wherein R1, R2, Ar, A, X, Y, Z, m and n are each, as defined in claim 1, comprising: (1) subjecting a compound of the following formula: or a salt thereof to the removal reaction of the protective carboxy group, in order to provide a compound of the following formula: Rl-X-Ar- (CH2) m / ^ V ^ (CH2) n -COOH (I-b) or a salt thereof; u (2) oxidizing the vinyl group of a compound having the following formula: or a salt thereof, so as to provide a compound of the above-mentioned formula (I-b) or a salt thereof; or (3) reduce a compound of the following formula: Y. JL Rl-X-Ar- (CH2) rn CH2) n "* 2 M ~ c) or a salt thereof, so as to provide a compound having the following formula: or a salt thereof; or (4) carrying out the reaction of a compound having the formula (Ib) mentioned above or its reactive derivative in the carboxy group, or a salt thereof, with a compound of the following formula: NH2-OR3 (IV) or its reactive derivative in the amino group, or a salt thereof, so as to provide a compound having the formula indicated below: or a salt thereof; or (5) cyclizing a compound of the following formula: (i ??: Rl or a salt thereof, so as to provide a compound of the following formula: R! -X-Ar- (CH2) m • CH2-R2 or a salt thereof; or (6) carrying out the reaction of a compound of the formula (Ib) mentioned above or its reactive derivative in the carboxy group, or a salt thereof, with an optically active amine or its reactive derivative in the amino group, or a salt thereof, so as to provide a compound of the following formula: or a salt thereof; or (7) submitting a compound having the following formula Rl-X-Ar-n-C0NH-0R3 (I-h) or a salt thereof to the removal reaction of the protective hydroxy group, to provide a compound having the following formula: (i-i: íl-X-Ar- (CH2) m X ', CH2) n-C0NHOH or a salt thereof; u (8) oxidize a compound of the following formula or a salt thereof, to provide the compound of the following formula: or one of its salts; or (9) carrying out the reaction of a compound of the above-mentioned formula (I-c) or a salt thereof, with a compound having the following formula: to provide a compound having the following formula: Rl-X-Ar- (CH2) m .x- X.; CH2) n- 2 (l-l) or a salt thereof; or (10) carrying out the reaction of a compound of the following formula: or a salt thereof, with a compound of the following formula: R ^ X-Ar-ICH ^ m1_1 (VII) or a salt thereof, so as to provide a compound of the following formula: or a salt thereof; or (11) cyclizing a compound having the following formula: or a salt thereof, to provide a compound of the following formula: ~ --- or a salt of it; or (12) carrying out the reaction of a compound of the following formula: (IX) Rl-X-Ar- (CH2) m '(CH2) n-R2 or a salt thereof, with a compound of the following formula: HS-A-SH (X) in order to provide a compound of the following formula: Rl-X-Ar- (CH2! M ~ (CH2) n-R2 I-o] or a salt thereof; or (13) amidating a compound of the following formula; n-R2 or its reactive derivative in the carboxy group, or a salt thereof, so as to provide a compound of the following formula: Rl-X-Ar- (CH2 ^ m X, CH2) n "R2 d-q) or a salt thereof; or 10 (14) acylating a compound of the following formula: Rl-X-Ar- (CH2) m X, CH2) n- 2 I-r) Or its reactive derivative in the amino group, or a salt thereof, in order to provide a compound having the or one of its salts, or (15) submit a compound that has the following 25 formula: ^ ßümÚiU ^ Éit ^ -i or a salt thereof to a removal reaction of the protective amino group, in order to provide a compound of the formula: or a salt thereof; or (16) submit a compound of the following formula: or one of its salts to a removal reaction of the hydroxy protecting group, in order to provide a compound of the formula: or a salt thereof; u (17) oxidizing a compound having the following formula: or a salt thereof, so as to provide a compound of the formula: or one of its salts; or 18) reduce a compound of the formula: or a salt thereof, so as to provide a compound of the following formula: Rl-X-Ar- (CH2) m-X, (CH2) n-R2 I-z] or a salt thereof; u (19) oxidizing a compound of the following formula: Rl-X-Ar- (CH2) n- 2 (I-aa) or a salt thereof, so as to provide a compound having the following formula: or a salt thereof; or (20) acylating a compound of the following formula: or a salt thereof, so as to provide a compound having the following formula: (I-ac) or a salt thereof; or (21) carrying out the reaction of a compound of the following formula: or a salt thereof, with a compound having the following formula: Rx-L (XII) or a salt thereof, so as to provide a compound having the following formula: or a salt thereof; or (22) submit a compound of the following formula: and) or a salt thereof, to a removal reaction of the protective carboxy group, in order to provide a compound having the following formula: or a salt thereof; or (23) carrying out the reaction of a compound of the formula: Rl-X-Ar- (CH2 pr> (CH2) n-R2 M-af) or a salt thereof, with a substituted amine, so as to provide the compound of the following formula: Rl-X- Ar- (CH2) m / (CH2) n- 2 (I ~ a < 3) or a salt thereof, wherein R1, R2, Ar, A, X, Y, Z, and m are each, as mentioned above, Rxa is haloaryl or halo, Rxb aryl, R1C is aryl at least substituted by optionally substituted aryl R1d is aryl having at least one carboxy portion, Rxß is aryl having at least one amido moiety, R- ^ is aryl having at least one amino moiety, Rxg is aryl having at least one amino moiety an acylamino moiety, RLh is aryl having at least one protected amino moiety, RL is aryl having at least one protected hydroxy moiety, R11 is aryl having at least one hydroxy moiety, R1k is aryl having at least one a thio moiety, R1I is aryl having at least one sulfinyl or sulfonyl moiety, R1 ,, is aryl having at least one formyl moiety, R1 ,, is aryl having at least one hydroxymethyl moiety, Rxc is aryl having at least one vinyl moiety, Rxp is aryl having at least one portion 1,2-dihydroxyethyl, R1q is aryl having at least one acyloxy portion, RLr is aryl having at least one protected carboxy moiety, R1 is aryl having at least one haloalkanoyl (lower) moiety, RM is aryl having at least one substituted (lower) amino alkanoyl moiety, R is protected carboxy, R 2b is optically active amide, R C is protected carboxy, R 3 is hydrogen or protective hydroxy group, R 3a is protective hydroxy group, R 4 is optionally substituted aryl R 5 and R6 are each hydrogen or combine together to form lower alkylene, is already thio, sulfinyl or sulfonyl, Za is methylene, thio, sulfinyl or sulfonyl which provide at least one Ya and Z- whether thio or sulfinyl, Yb is thio, sulfinyl or sulfonyl, Zb is methylene, thio, sulfinyl or sulfonyl which provide at least one Yb and Zb which is sulfinyl or sulfonyl, L is a leaving group, and m1 is an integer of 1 and 6. 11. - Pharmaceutical compositions comprising u The compound of claim 1 or a pharmaceutically acceptable salt and a pharmaceutically acceptable excipient or carrier. 12. Process for preparing pharmaceutical compositions comprising mixing the compound according to claim 1, or a pharmaceutically acceptable salt, with a pharmaceutically acceptable excipient or carrier. 13. Use of a compound according to claim 1, or a pharmaceutically acceptable salt, which is in the form of a medicament. 14. Use of a compound according to claim 1, or of a pharmaceutically acceptable salt, which is in the form of matrix metalloproteinase inhibitor (MMP) or tumor necrosis factor (TNF a). 15. - Use of a compound according to claim 1, or a pharmaceutically acceptable salt, which comprises making medicaments for the treatment and / or prevention of diseases mediated by MMP or TNF a. 16. - Method for treating and / or preventing diseases mediated by MMP or TNF comprising the administration of a compound of claim 1, or of a pharmaceutically acceptable salt, to a human or an animal. 17. - Use of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, comprising the treatment and / or prevention of diseases mediated by MMP or TNF.